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Georges F Hatoum,1,* H Thomas Temple,2,* Silvio A Garcia,1 Yi Zheng,1,3 Fouad Kfoury,4 Jill Kinley,5 Xiaodong Wu1,3 1Department of Radiation Oncology, HCA Florida JFK Medical Center Comprehensive Cancer Institute, Lake Worth, FL, USA; 2Department of Orthopedic Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; 3Department of Research and Development, Executive Medical Physics Associates, North Miami Beach, FL, USA; 4Pharmacy Department, South Miami Hospital, South Miami, FL, USA; 5Department of Clinical Research, HCA Florida JFK Medical Center, Atlantis, FL, USA*These authors contributed equally to this workCorrespondence: Xiaodong Wu, Executive Medical Physics Associates, 19470 NE 22nd Road, North Miami Beach, FL, 33179, USA, Tel +1 305 775 0333, Email drxiaodongwu@yahoo.comPurpose: To report a case of large extremity soft tissue sarcoma (2933 cc), safely treated with a novel approach of interdigitating high-dose LATTICE radiation therapy (LRT) with standard radiation therapy as a neoadjuvant treatment to surgery.Patients and Methods: Four sessions of high-dose LRT were delivered in a weekly interval, interdigitated with standard radiation therapy. The LRT plan consisted of 15 high-dose vertices receiving a dose > 12 Gy per session, with 2– 3 Gy to the peripheral margin of the tumor. The patient underwent surgical excision 2 months after the new regimen of induction radiation therapy.Results and Discussion: The patient tolerated the radiation therapy regimen well. The post-operative assessment revealed a negative surgical margin and over 95% necrosis of the total tumor volume. The post-surgical wound complication was mitigated by outpatient wound care. Interdigitating multiple sessions of high-dose LATTICE radiation treatments with standard neoadjuvant radiation therapy as a neoadjuvant therapy for soft tissue sarcoma was feasible and did not incur additional toxicity in this clinical case. A phase-I/II trial will be conducted to further evaluate the toxicity and efficacy of the new treatment strategy with the intent to increase the rate of pathologic necrosis, which has been shown to positively correlate with the overall survival.Keywords: sarcoma, SFRT, LATTICE radiotherapy, LRT, chemotherapy, surgery, necrosis

Christopher M Aguila,1 Gaëtan J-R Delcroix,2–5 David N Kaimrajh,6 Edward L Milne,6 H Thomas Temple,5,7 Loren L Latta2,6 1Department of Biological Sciences, Florida International University, Miami, FL, USA; 2Department of Orthopaedics, Miller School of Medicine, University of Miami, Miami, FL, USA; 3Research Service & Geriatric Research, Education, and Clinical Center, Bruce W. Carter Veterans Affairs Medical Center, Miami, FL, USA; 4Interdisciplinary Stem Cell Institute, University of Miami, Miami, FL, USA; 5Vivex Biomedical Inc., Marietta, GA, USA; 6Max Biedermann Institute for Biomechanics, Miami Beach, FL, USA; 7Translational Research and Economic Development, Nova Southeastern University, Fort-Lauderdale, FL, USA Purpose: This study was designed to investigate the biomechanical properties of nonirradiated (NI) and irradiated (IR) peroneus tendons to determine if they would be suitable allografts, in regards to biomechanical properties, for anterior cruciate ligament reconstruction after a dose of 1.5–2.5 Mrad.Methods: Seven pairs of peroneus longus (PL) and ten pairs of peroneus brevis (PB) tendons were procured from human cadavers. The diameter of each allograft was measured. The left side of each allograft was IR at 1.5–2.5 Mrad, whereas the right side was kept aseptic and NI. The allografts were thawed, kept wet with saline, and attached in a single-strand fashion to custom freeze grips using liquid nitrogen. A preload of 10 N was then applied and, after it had reached steady state, the allografts were pulled at 4 cm/sec. The parameters recorded were the displacement and force.Results: The elongation at the peak load was 10.3±2.3 mm for the PB NI side and 13.5±3.3 mm for the PB IR side. The elongation at the peak load was 17.4±5.3 mm for the PL NI side and 16.3±2.0 mm for the PL IR side. For PL, the ultimate load was 2,091.6±148.7 N for NI and 2,122.8±380.0 N for IR. The ultimate load for the PB tendons was 1,485.7±209.3 N for NI and 1,318.4±296.9 N for the IR group. The ultimate stress calculations for PL were 90.3±11.3 MPa for NI and 94.8±21.0 MPa for IR. For the PB, the ultimate stress was 82.4±19.0 MPa for NI and 72.5±16.6 MPa for the IR group. The structural stiffness was 216.1±59.0 N/mm for the NI PL and 195.7±51.4 N/mm for the IR side. None of these measures were significantly different between the NI and IR groups. The structural stiffness was 232.1±45.7 N/mm for the NI PB and 161.9±74.0 N/mm for the IR side, and this was the only statistically significant difference found in this study (P=0.034).Conclusion: Our statistical comparisons found no significant differences in terms of elongation, ultimate load, or ultimate stress between IR and NI PB and PL tendons. Only the PB structural stiffness was affected by irradiation. Thus, sterilizing allografts at 1.5–2.5 Mrad of gamma irradiation does not cause major alterations in the tendons’ biomechanical properties while still providing a suitable amount of sterilization for anterior cruciate ligament reconstruction. Keywords: ACL reconstruction, allograft, sterilization, tissue banking

Unlabelled: The need for segmental resection versus intralesional treatment of low-grade chondrosarcomas of the appendicular skeleton remains controversial. We hypothesized extended intralesional treatment would equally control malignant disease but with improved functional outcomes and decreased postoperative complications. We retrospectively reviewed 31 patients with 32 Grade I intracompartmental chondrosarcomas of the long bones of the appendicular skeleton treated with either resection (15 lesions) or extended intralesional curetting (17) at a minimum followup of 2 years (median, 55 months; range, 24-203 months). Lesions were larger and median followup was longer in the resection cohort. One local recurrence developed in each treatment cohort and neither transitioned to a higher grade of tumor. No patient had metastases develop or died of disease. The mean final Musculoskeletal Tumor Society functional scores were greater after extended intralesional versus resection treatment (29.5 versus 25.1). Complications were observed more frequently after resection and reconstruction (seven of 15) as compared with extended intralesional treatment (one of 17). Extended intralesional treatment of Grade I intracompartmental chondrosarcomas of the long bones of the appendicular skeleton therefore appears safe with improved functional scores and decreased complications versus segmental resection and reconstruction.Level Of Evidence: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Several variables have been reported as being prognostic with regard to the outcomes of soft-tissue sarcomas. Although the tumors are subjectively ominous, no prior study has been performed to evaluate the treatment or prognosis of fungating soft-tissue sarcomas.Methods: We performed a retrospective review of all soft-tissue sarcomas treated at our institution between 1989 and 2004 that had been followed for a minimum of two years or until the death of the patient. Our study group consisted of twenty-four patients with a primary high-grade fungating tumor, and our control group consisted of 146 consecutive patients with a primary high-grade non-fungating tumor. The study cohorts were compared with regard to disease presentation, treatment, and oncologic outcomes.Results: There were no significant differences in tumor size, tumor depth, or histopathologic diagnoses between the cohorts, although the patients with a fungating tumor tended to be older (mean, sixty-five years compared with fifty-five years in the control group; p = 0.004) and have shorter postoperative follow-up (mean, thirty-eight months compared with sixty-five months in the control group; p = 0.03). The proportion of patients presenting with metastases was significantly greater in the group with a fungating tumor (33% compared with 9% in the control group; p = 0.003). Significantly more patients with a fungating tumor underwent amputation (35% compared with 12% in the control group; p = 0.01), while a greater proportion of control patients received radiation therapy (68% compared with 39% in the group with a fungating tumor; p = 0.02). There was no difference in the proportions of patients receiving chemotherapy or in the local recurrence rates between the two cohorts. The Kaplan-Meier five-year overall survival estimates were 20% in the group with a fungating tumor compared with 63% (p < 0.0001) in the control group. The Kaplan-Meier five-year disease-specific survival estimates for patients presenting with localized disease was 58% in the group with a fungating tumor and 74% in the control group (p = 0.05). Multivariate analysis demonstrated that disease stage, fungation, and a tumor size of > or = 10 cm were significant independent negative prognostic factors for disease-specific survival.Conclusions: Malignant tumor ulceration is an independent predictor of a poor prognosis for patients with a high-grade soft-tissue sarcoma. Despite the discouraging overall prognosis, aggressive multidisciplinary treatment can lead to long-term survival in an important subgroup of patients with fungating lesions. [ABSTRACT FROM AUTHOR]

Background: Foot and ankle sarcomas have historically been treated with amputation because of the difficulty in achieving local disease control and maintaining a functional foot. Potential opportunities for limb salvage may be further compromised by unplanned excisions. Materials and Methods: We reviewed 52 consecutive patients with soft tissue sarcomas of the foot and ankle and analyzed the impact of planned versus unplanned initial excision, limb salvage, and multimodality therapy on treatment and outcomes. Results: Unplanned excisions had been performed in 29 (55.8%) patients. Limb salvage was performed in 38 patients, with 14 requiring free soft tissue transfers. At an average followup of 99 (range, 24 to 216) months, the 5-year overall survival estimate was 76.3%. Although not statistically significant, we noted clinically relevant potential differences in local recurrence-free, disease-free, and oncologic survival between the planned and unplanned excision groups. Seven patients (13.5%) had a local recurrence, five of these following an unplanned excision. Functional scores averaged 83.2% for all patients which were similar between planned versus unplanned and amputation versus limb salvage groups. Significantly more patients with unplanned excisions required free flaps for limb salvage (p = 0.017) and received adjuvant radiotherapy (p = 0.0004). Conclusion: Unplanned surgery for soft tissue sarcomas of the foot and ankle often results in the need for more aggressive surgery and/or adjuvant radiotherapy and may impact oncologic outcomes, but does not necessarily portend worse functional outcomes. Multimodal therapy and judicious use of soft tissue flap reconstruction allows limb salvage in most patients with favorable outcomes. [ABSTRACT FROM AUTHOR]

Background: Metastatic disease of the skeleton occurs in at least 20% to 30% of patients with malignancy, but metastasis to the foot and hand (acrometastasis) is extremely rare (0.007% to 0.3%). Metastases to the feet are even rarer and have been reported in half to one-third the rate for hand metastases. Failure to recognize these lesions has led to delayed diagnosis and/or inappropriate treatment. The purpose of this report is to highlight the clinical and radiologic features that aid in the diagnosis and potential treatment of this condition along with a pertinent review of the literature. Materials and Methods: In a retrospective review of 694 patients with histologically proven metastatic skeletal disease (January 1988 to January 2007), 14 cases of metastatic lesions to the foot were identified. Results: The most frequent primary site was in the genito-urinary system in eight patients and the most common bones involved were the calcaneus and the talus in six patients each. All patients died after a mean survival of 14.8 (range, 1 to 54) months after diagnosis of metastases. Conclusion: Although metastatic disease of the foot is rare, it should be considered in the diagnosis of a painful foot, especially if suspicious radiographic changes are present in an older patient. The common primary sites are the genito-urinary, lungs, breast, and the colo-rectum. Treatment is usually palliative to reduce pain and maintain function. [ABSTRACT FROM AUTHOR]

Osteoarticular allografts can be used for limb reconstruction following tumor excision. Most commonly, the distal femur, proximal tibia and distal radius have been studied, while distal tibial allografts receive only sporadic mention in the literature. We evaluated the functional outcomes of distal tibial allografts used in tumor reconstruction. Following FDA guidelines and using a questionnaire, we surveyed operating surgeons on the outcomes of 29 distal tibial allografts used to reconstruct osseous defects secondary to benign and malignant tumors. Twelve patient questionnaires were returned revealing nine complications in eight patients. These included nonunions (three), fracture (two), arthrosis (two), and delayed union (two). There were no reported infections. Two patients died of their disease. The average rating using the Musculoskeletal Tumor Society (MSTS) score was 67.3%. The 10 living patients had an average rating of 72.4%. Distal tibial osteoarticular allografts offer acceptable functional results when used in tumor reconstruction. Difficulties achieving union (delayed or nonunion) between the host and the graft appears the most common complication of this technique. [ABSTRACT FROM AUTHOR]

Background: Sacral chordoma is a rare, low to intermediate-grade tumor that poses substantial challenges in terms of timely diagnosis and adequate treatment. Few studies have examined the oncologic and functional outcomes of patients treated for sacral chordoma.Methods: The clinical records of sixteen patients who had undergone sacrectomy for chordoma between 1985 and 2001 were evaluated retrospectively. All patients underwent resection by means of a sequential combined anterior and posterior approach. Patients were followed clinically at six-month intervals following recovery from the index surgical procedure. The disease onset, treatment, hospital stay, recurrence rates, survival, adjuvant therapy, functional outcome measures, and complications were evaluated.Results: The average age at the time of diagnosis was sixty-one years. The mean tumor size was 15.2 cm in diameter, and all patients had a resection involving S1 or S2. The mean duration of follow-up was sixty-six months, and the tumor recurred in twelve of the sixteen patients. The mean time to metastasis was fifty months. Four patients were clinically disease-free at a mean follow-up of 94.5 months, while five patients died as a result of progressive local or metastatic disease at a mean follow-up of 31.4 months. Only one patient had normal bowel and bladder control postoperatively, and only three were able to walk without assistive devices. Eight patients had wound complications, and one patient had a deep-vein thrombosis. With the numbers available, neither negative margins at the time of initial tumor resection nor adjuvant radiation therapy had a significant impact on survival or local recurrence. More cephalad levels of resection were associated with significantly worse bowel (p = 0.01) and bladder (p = 0.01) control. Complications were frequent and were more common with a larger tumor size at the time of presentation (p = 0.034).Conclusions: The treatment of sacral chordoma is an arduous clinical undertaking that requires a multidisciplinary approach and attention to detail from the outset. Despite aggressive well-planned surgical management and adherence to strict surveillance protocols, frequent recurrence and the late onset of metastatic disease are to be expected in a substantial proportion of patients, especially those with a very large chordoma or one at a more cephalad level. Adequate surgical treatment results in substantial functional impairment and numerous complications; however, it does offer the possibility of long-term disease-free survival. We advocate an attempt at complete resection, when there is still a possibility of cure, and aggressive treatment of local recurrences.Level Of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the clinical and oncologic outcomes of high-dose brachytherapy (BRT) versus both preoperative and postoperative external beam radiation therapy (EBRT) in the setting of high-grade soft tissue sarcoma., Methods: This is a retrospective cohort study of 144 patients treated surgically for soft tissue sarcoma at the same institution from 2010 to 2021. Patients treated for a soft tissue sarcoma with surgery and radiation therapy in the form of BRT, Neoadjuvant EBRT (Neo-EBRT) or adjuvant EBRT (AD-EBRT) were included., Results: 56 patients were treated with BRT, 42 with Neo-EBRT, and 46 with AD-EBRT. There was a greater incidence of grouped wound complications in Neo-EBRT with 50% compared to both BRT with 25% and AD-EBRT with 28.3% (p = 0.02). Univariate and multivariate analysis showed that there was an increased risk of wound complications with Neo-EBRT when compared to brachytherapy (p = 0.03 and p = 0.007, respectively). Univariate and multivariate analysis showed that there was no difference in risk of LR between treatment groups (p = 0.28)., Conclusion: Brachytherapy is a valuable treatment modality that offers clinical and logistical advantages when compared to the conventional Neo-EBRT in soft tissue sarcomas. Brachytherapy offers a lower risk of wound complications and a comparable local control. This manuscript presents decision-making strategies for determining the appropriate radiation modality for specific circumstances., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Limb salvage surgeries utilizing endoprostheses and allografts are performed for a variety of oncologic conditions. These reconstructions can fail and require revision for many reasons, which are outlined and classified into mechanical failures (soft tissue failures, aseptic loosening, structural failure), non-mechanical failures (infection, tumor progression), and pediatric failures (physeal arrest, growth dysplasia). Distinct radiologic and clinical findings define specific failure subtypes but are sparsely illustrated in the radiology literature. Specifically, an understanding of the organizational structure of the failure modes can direct radiologists' search for post-reconstruction complications, enhance an appreciation of their prognostic significance, and facilitate research by standardizing the language and conceptual framework around outcomes. The purpose of this review is to highlight the key radiologic findings and imaging studies of each failure mode in orthopedic oncologic reconstructive surgery in the context of risk factors, failure rates, prognosis and survival statistics, and clinical decision-making regarding chemotherapy, radiation, and revision surgery.

Introduction: A Brodie's abscess is a form of subacute osteomyelitis that is often considered in the differential diagnosis of other benign and malignant bone lesions. The authors summarize the findings of five cases of Brodie's abscesses in the distal tibia initially thought to be tumors by the referring physicians., Case Report: All five cases were presented to the referring physicians with a chief complaint of ankle pain. All patients complained of chronic ankle pain and swelling that was aggravated by activity without constitutional symptoms. On physical examination, all patients presented with point tenderness over the distal tibia/malleolar regions. Three out of the five cases had a full range of ankle motion; the other two had limited dorsiflexion secondary to pain. All inflammatory laboratory values were within normal limits or only slightly elevated. All initial radiographs of the cases described demonstrated a well-defined radiolucent lesion within the distal tibia. In all cases, patients were treated with curetting, with or without bone graft. Bacterial and fungal cultures were negative in all five patients and no long-term post-operative antibiotics were administered., Conclusion: In this report, we discuss the clinical, radiographic, and pathologic features of this relatively rare condition in the distal tibia. The distinct clinicopathologic features of the disease process are presented to distinguish Brodie's abscess from a bone tumor., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Objectives: Because size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity., Methods: This IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters., Results: Median patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12)., Conclusions: Analysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability., Competing Interests: JT: advisory or consulting role with Novartis, Lilly, Janssen, Blueprint Medicines, Deciphera, Daiichi Sankyo, Epizyme, Agios, C4 Therapeutics, Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Souza, D’Amato, Jonczak, Costa, Trent, Rosenberg, Yechieli, Temple, Pattany and Subhawong.)

Background: We developed a novel, injectable and decellularized human peripheral nerve-based scaffold, named Micronized Human Neural Tissue (hMINT), designed to be used as a supportive matrix for stem cell transplantation in the context of spinal cord injury (SCI)., Materials and Methods: Human donated sciatic nerves were micronized at liquid nitrogen temperature prior to decellularization using 3 different procedures of various harshness. hMINT were characterized in terms of particle size, DNA, sulfated glycosaminoglycans (sGAG) and growth factors content. To test the biocompatibility and bioactivity of the various preparations, we used a type of mesenchymal stromal cells (MSCs), termed MIAMI cells, which were placed in contact with hMINT to monitor cell attachment by confocal microscopy and gene expression by RT-qPCR in vitro., Results: The content of DNA, sGAG and growth factors left in the product after processing was highly dependent on the decellularization procedure used. We demonstrated that hMINT are biocompatible and promoted the attachment and long-term survival of MIAMI cells in vitro. Finally, combination with hMINT increased MIAMI cells mRNA expression of pro-survival and anti-inflammatory factors. Importantly, the strongest bioactivity on MIAMI cells was observed with the hMINT decellularized using the mildest decellularization procedure, therefore emphasizing the importance of achieving an adequate decellularization without losing the hMINT's bioactivity., Perspectives and Clinical Significance: The capacity of hMINT/stem cells to facilitate protection of injured neural tissue, promote axon re-growth and improve functional recovery will be tested in an animal model of SCI and other neurodegenerative disorders in the future., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Liposarcoma is the most commonly diagnosed subtype of soft tissue sarcoma. As these tumors often arise near vital organs and neurovascular structures, complete resection can be challenging; consequently, recurrence rates are high. Additionally, available chemotherapeutic agents have shown limited benefit and substantial toxicities. There is, therefore, a clear and unmet need for novel therapeutics for liposarcoma. Discoidin domain receptor tyrosine kinase 1 (DDR1) is involved in adhesion, proliferation, differentiation, migration, and metastasis in several cancers. However, the expression and clinical importance of DDR1 in liposarcoma are unknown., Questions/purposes: The purposes of this study were to assess (1) the expression, (2) the association between DDR1 and survival, and (3) the functional roles of DDR1 in liposarcoma., Methods: The correlation between DDR1 expression in tumor tissues and clinicopathological features and survival was assessed via immunohistochemical staining of a liposarcoma tissue microarray. It contained 53 samples from 42 patients with liposarcoma and 11 patients with lipoma. The association between DDR1 and survival in liposarcoma was analyzed by Kaplan-Meier plots and log-rank tests. The DDR1 knockout liposarcoma cell lines were generated by CRISPR-Cas9 technology. The DDR1-specific and highly selective DDR1 inhibitor 7RH was applied to determine the impact of DDR1 expression on liposarcoma cell growth and proliferation. In addition, the effect of DDR1 inhibition on liposarcoma growth was further accessed in a three-dimensional cell culture model to mimic DDR1 effects in vivo., Results: The results demonstrate elevated expression of DDR1 in all liposarcoma subtypes relative to benign lipomas. Specifically, high DDR1 expression was seen in 55% (23 of 42) of liposarcomas and no benign lipomas. However, DDR1 expression was not found to be associated with poor survival in patients with liposarcoma. DDR1 knockout or treatment of 7RH showed decreased liposarcoma cell growth and proliferation., Conclusion: DDR1 is aberrantly expressed in liposarcoma, and it contributes to several markers of oncogenesis in these tumors., Clinical Relevance: This work supports DDR1 as a promising therapeutic target in liposarcoma., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Competing Interests: The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request.

Background: Surgical site infection (SSI) after segmental endoprosthetic reconstruction in patients treated for oncologic conditions remains both a devastating and a common complication. The goal of the present study was to identify variables associated with the success or failure of treatment of early SSI following the treatment of a primary bone tumor with use of a segmental endoprosthesis., Methods: The present study used the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) data set to identify patients who had been diagnosed with an SSI after undergoing endoprosthetic reconstruction of a lower extremity primary bone tumor. The primary outcome of interest in the present study was a dichotomous variable: the success or failure of infection treatment. We defined failure as the inability to eradicate the infection, which we considered as an outcome of amputation or limb retention with chronic antibiotic suppression (>90 days or ongoing therapy at the conclusion of the study). Multivariable models were created with covariates of interest for each of the following: surgery characteristics, cancer treatment-related characteristics, and tumor characteristics. Multivariable testing included variables selected on the basis of known associations with infection or results of the univariable tests., Results: Of the 96 patients who were diagnosed with an SSI, 27 (28%) had successful eradication of the infection and 69 had treatment failure. Baseline and index procedure variables showing significant association with SSI treatment outcome were moderate/large amounts of fascial excision ≥1 cm2) (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.001), use of local muscle/skin graft (OR,11.88 [95% CI, 1.83 to 245.83]; p = 0.031), and use of a deep Hemovac (OR, 0.24 [95% CI, 0.05 to 0.85]; p = 0.041). In the final multivariable model, excision of fascia during primary tumor resection was the only variable with a significant association with treatment outcome (OR, 10.21 [95% CI, 2.65 to 46.21]; p = 0.018)., Conclusions: The results of this secondary analysis of the PARITY trial data provide further insight into the patient-, disease-, and treatment-specific associations with SSI treatment outcomes, which may help to inform decision-making and management of SSI in patients who have undergone segmental bone reconstruction of the femur or tibia for oncologic indications., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H576)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Aneurysmal bone cyst (ABC) is a benign but locally aggressive lesion that predominantly affects children and young adults. ABC, which accounts for approximately 70% of the cases, is now recognized to be a true neoplasm, whereas ABC-like changes associated to other bone neoplasms (also referred in the literature as secondary ABC) accounts for the remaining 30%. The solid variant of ABC is also considered a true neoplasm but is rare. ABC can involve any bone in the body, and although it has a metaphyseal preference, it can involve any part of a bone and soft tissues. As with any bone tumor, the initial evaluation of ABCs should be done with radiographs followed by magnetic resonance imaging or less frequently computed tomography for further characterization. The imaging appearance of ABC is variable; however, a lytic and expansile lesion with fluid-fluid levels is the most common presentation. The main differential diagnosis of an ABC in the pediatric population is unicameral bone cyst (UBC) and telangiectatic osteosarcoma, therefore a biopsy is recommended before treatment. The therapeutic options of ABC range from curettage with or without adjuncts such as phenol, liquid nitrogen, argon laser and bone grafting or bone substitutes to more recently employed alternatives such as image-guided sclerotherapy with various sclerosing agents and monoclonal antibodies (e.g., Denosumab)., (© 2022. The Author(s).)

Background: Cellular allogeneic bone grafts are used as a biologic adjuvant in lumbar spinal fusions. The clinical use of a minimally invasive extreme lateral approach to the lumbar spine has been widely adopted; however, there are few clinical studies that have documented the clinical and radiographic outcomes associated with the use of cellular allografts as an adjunct to fusion in this advanced surgical approach., Methods: A consecutive series of 67 patients (34 males and 33 females) with a mean age of 66.8 years (26-85 years) who underwent single- or multilevel lateral lumbar interbody fusion (LLIF) with supplemental posterior segmental spinal fixation using a cellular allogeneic bone matrix as the only bone graft material was retrospectively reviewed by a single surgeon. Patients' preoperative and 3- and 12-month postoperative data were studied. All patients were followed for a minimum of 12 months. Standardized clinical outcome measures-36-Item Short Form Surgery (SF-36), Oswestry Disability Index (ODI), and visual analog scale (VAS) back and leg pain scores-were used to evaluate the clinical outcomes. An average of 2.25 levels was treated per patient (151 total levels). Fusion status was assessed by dynamic radiographs and computed tomography (CT) scans. The statistical method used to identify the significance of the observed changes in clinical outcomes was the paired 2-sided t -tests. Significance was ascribed to P values <0.05., Results: Fusion was achieved at 142 levels (142/151; 94%). Eight levels (8/151; 5.3%) showed partial fusions and one patient (single level) had no fusion. In the group of patients with fusions, the mean back and leg pain scores showed improvement from preoperative scores at both 3 and 12 months (P<0.001). Functional outcomes showed similar clinical success in both in SF-36 and ODI scores., Conclusions: The use of a cellular allogeneic bone matrix provided osteoconductive and osteoinductive components for successful spine fusions and was associated with statistically significant improvement in SF-36, VAS, and ODI scores., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jss-21-28). TCT, MD, is shareholder, royalty earner, consultant, and married to employee of VIVEX Biologics, Inc.; HTT, MD, is the Chief Medical Officer and Medical Director of VIVEX Biologics, Inc.; JKB, MD, is a consultant with VIVEX Biologics, Inc. The authors have no conflicts of interest to declare., (2021 Journal of Spine Surgery. All rights reserved.)

Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. The author certifies that neither he, nor any member of his immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.

Background: Aseptic loosening is one of the most common causes of revision of distal femoral endoprostheses and is considered a mid- to long-term complication. There are not many reports of 10-year survivorship free from aseptic loosening and all-cause survivorship in cemented stems. To our knowledge, there are no reports on radiographic features that are associated with aseptic loosening of these implants., Questions/purposes: (1) What is the 5- and 10-year survivorship free from aseptic loosening in patients undergoing reconstruction with a cemented distal femoral endoprosthesis after a tumor resection? (2) What is the all-cause 5- and 10-year survivorship at in these patients? (3) What radiographic features are associated with aseptic loosening at long-term follow-up?, Methods: We performed a multicenter retrospective study reviewing aseptic loosening in cemented prostheses to determine radiographic features associated with long-term implant survivorship. Patients who underwent a cemented distal femoral reconstruction with a modular endoprosthesis after resection of a musculoskeletal tumor between 1997 and 2017 were reviewed. A total of 246 patients were identified from five institutions and met initial inclusion criteria. Of those, 21% (51) were lost to follow-up before 2 years, leaving 195 patients available for us to evaluate and analyze the survivorship and radiologic features associated with long-term implant survival. The mean (range) follow-up was 78 months (22 to 257). At the time of this analysis, 69% (135 of 195) of the patients were alive. Osteosarcoma was the most common diagnosis in 43% of patients (83 of 195), followed by metastatic carcinoma 13% (25 of 195). Fifty-six percent (110 of 195) of patients received chemotherapy; 15% (30 of 195) had radiation therapy. Aseptic loosening was diagnosed radiographically and was defined as a circumferential radiolucent line on all views, or subsidence around the stem in the absence of infection. We present 5- and 10-year Kaplan-Meier survivorship free from aseptic loosening, 5- and 10-year all-cause survivorship, and a qualitative assessment of radiographic features potentially associated with aseptic loosening (including the junctional radiolucent area, and cortical expansion remodeling). The junctional radiolucent area was defined as a radiolucent area of the bone starting at the bone-endoprosthesis junction to the tip of the femoral stem, and cortical expansion remodeling was defined as an increased cortical thickness at the stem tip. Although we wished to statistically analyze radiographic factors potentially associated with aseptic loosening, we did not have enough clinical material to do so (only nine patients developed loosening). Instead, we will report a few preliminary qualitative observations, which necessarily are preliminary, and which will need to be confirmed or refuted by future studies. We urge caution in interpreting these findings because of the very small numbers involved., Results: Kaplan-Meier survivorship free from aseptic loosening of the femoral component at 5 and 10 years were 95% (95% CI 89 to 98) and 93% (95% CI 86 to 97), respectively. Kaplan-Meier survivorship free from revision for any cause at 5 and 10 years were 74% (95% CI 65 to 79) and 64% (95% CI 49 to 70), respectively. Although the numbers were too small to analyze statistically, all patients with aseptic loosening had a junctional radiolucent area more than 20% of the total length of the stem without cortical expansion remodeling at the stem tip. No aseptic loosening was observed if there was cortical ex remodeling, a junctional radiolucent area less than 20%, or curved stems that were 13 mm or greater in diameter. The numbers of patients with aseptic loosening in this series were too small to analyze statistically., Conclusions: Cemented distal femoral endoprostheses have a relatively low rate of aseptic loosening and acceptable projected first-decade survivorship. The presence of a radiolucent area more than 20% without cortical expansion remodeling at the stem tip may lead to aseptic loosening in patients with these implants. Close radiographic surveillance and revision surgery may be considered for progressive lucencies and clinical symptoms of pain. If revision is contemplated, we recommend using larger diameter curved cemented stems. These are preliminary and provisional observations based on a low number of patients with aseptic loosening; future studies with greater numbers of patients are needed to validate or refute these findings., Level of Evidence: Level III, therapeutic study.

Aims: The aticularis genu (AG) is the least substantial and deepest muscle of the anterior compartment of the thigh and of uncertain significance. The aim of the study was to describe the anatomy of AG in cadaveric specimens, to characterize the relevance of AG in pathological distal femur specimens, and to correlate the anatomy and pathology with preoperative magnetic resonance imaging (MRI) of AG., Methods: In 24 cadaveric specimens, AG was identified, photographed, measured, and dissected including neurovascular supply. In all, 35 resected distal femur specimens were examined. AG was photographed and measured and its utility as a surgical margin examined. Preoperative MRIs of these cases were retrospectively analyzed and assessed and its utility assessed as an anterior soft tissue margin in surgery. In all cadaveric specimens, AG was identified as a substantial structure, deep and separate to vastus itermedius (VI) and separated by a clear fascial plane with a discrete neurovascular supply. Mean length of AG was 16.1 cm ( ± 1.6 cm) origin anterior aspect distal third femur and insertion into suprapatellar bursa. In 32 of 35 pathological specimens, AG was identified (mean length 12.8 cm ( ± 0.6 cm)). Where AG was used as anterior cover in pathological specimens all surgical margins were clear of disease. Of these cases, preoperative MRI identified AG in 34 of 35 cases (mean length 8.8 cm ( ± 0.4 cm))., Results: AG was best visualized with T1-weighted axial images providing sufficient cover in 25 cases confirmed by pathological findings.These results demonstrate AG as a discrete and substantial muscle of the anterior compartment of the thigh, deep to VI and useful in providing anterior soft tissue margin in distal femoral resection in bone tumours., Conclusion: Preoperative assessment of cover by AG may be useful in predicting cases where AG can be dissected, sparing the remaining quadriceps muscle, and therefore function.Cite this article: Bone Joint Open 2020;1-9:585-593., Competing Interests: ICMJE COI statement: H. T. Temple reports consultancy, royalties, and stock/stock options from Vivex Biologics, employment by HCA Healthcare, grants/grants pending from Nova Southeastern University, and payment for lectures (including service on speakers bureaus), and for development of educational presentations from Stryker Orthopedics, all of which are unrelated to this article., (© 2020 Author(s) et al.)

Background: There is scant evidence to guide decision-making for patients considering total femoral replacement (TFR). We aimed to identify the indication, patient, disease, and surgical technique-related factors associated with failure. We hypothesized that failure occurs more frequently in the setting of revision surgical procedures, with infection as the predominant failure mode., Methods: We performed a retrospective cohort study of patients receiving total femoral endoprostheses for oncological and revision arthroplasty indications; 166 patients met these criteria. Our primary independent variable of interest was TFR for a revision indication (arthroplasty or limb salvage); the primary outcome was failure. Analyses were performed for patient variables (age, sex, diagnosis group, indication), implant variables (model, decade, length, materials), and treatment variables. We analyzed TFR failures with respect to patient factors, operative technique, and time to failure. We conducted bivariate logistic regressions predicting failure and used a multivariate model containing variables showing bivariate associations with failure., Results: Forty-four patients (27%) had treatment failure. Failure occurred in 24 (23%) of 105 primary TFRs and in 20 (33%) of 61 revision TFRs; the difference was not significant (p = 0.134) in bivariate analysis but was significant (p = 0.044) in multivariate analysis. The mean age at the time of TFR was 37 years in the primary group and 51 years in the revision group (p = 0.0006). Of the patients who had mechanical failure, none had reoccurrence of their original failure mode, whereas all 8 patients from the nonmechanical cohort had reoccurrence of the original failure mode; this difference was significant (p = 0.0001)., Conclusions: TFR has a high failure rate and a propensity for deep infection, especially in the setting of revision indications and prior infection. All failed TFRs performed for revision indications for infection or local recurrence failed by reoccurrence of the original failure mode and resulted in amputation., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Sarcomas are malignancies of mesenchymal origin that occur in bone and soft tissues. Many are chemo- and radiotherapy resistant, thus conventional treatments fail to increase overall survival. Natural Killer (NK) cells exert anti-tumor activity upon detection of a complex array of tumor ligands, but this has not been thoroughly explored in the context of sarcoma immunotherapy. In this study, we investigated the NK cell receptor/ligand immune profile of primary human sarcoma explants. Analysis of tumors from 32 sarcoma patients identified the proliferative marker PCNA and DNAM-1 ligands CD112 and/or CD155 as commonly expressed antigens that could be efficiently targeted by genetically modified (GM) NK cells. Despite the strong expression of CD112 and CD155 on sarcoma cells, characterization of freshly dissociated sarcomas revealed a general decrease in tumor-infiltrating NK cells compared to the periphery, suggesting a defect in the endogenous NK cell response. We also applied a functional screening approach to identify relevant NK cell receptor/ligand interactions that induce efficient anti-tumor responses using a panel NK-92 cell lines GM to over-express 12 different activating receptors. Using GM NK-92 cells against primary sarcoma explants ( n = 12) revealed that DNAM-1 over-expression on NK-92 cells led to efficient degranulation against all tested explants ( n = 12). Additionally, NKG2D over-expression showed enhanced responses against 10 out of 12 explants. These results show that DNAM-1 + or NKG2D + GM NK-92 cells may be an efficient approach in targeting sarcomas. The degranulation capacity of GM NK-92 cell lines was also tested against various established tumor cell lines, including neuroblastoma, Schwannoma, melanoma, myeloma, leukemia, prostate, pancreatic, colon, and lung cancer. Enhanced degranulation of DNAM-1 + or NKG2D + GM NK-92 cells was observed against the majority of tumor cell lines tested. In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1 + or NKG2D + GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies., (Copyright © 2020 Sayitoglu, Georgoudaki, Chrobok, Ozkazanc, Josey, Arif, Kusser, Hartman, Chinn, Potens, Pamukcu, Krueger, Zhang, Mardinoglu, Alici, Temple, Sutlu and Duru.)