http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Tue, 30 Apr 2013 10:47:39 +0000 http://www.hindawi.com/journals/srcm/2013/498604/ Unplanned excision of soft tissue sarcomas (STSs) outside comprehensive tumor management centers necessitates the need for wide reexcision to achieve adequate margins. We retrospectively reviewed medical records of 135 patients with STS operated at our hospital with the goal of examining outcomes, in terms of local recurrence (LR) and metastasis rate (MR), of reexcision following unplanned excision of STS and comparing results with those of first-time planned surgery. Eighty-four patients had their first-time surgery and 51 patients had come to us following unplanned excision at prereferral hospital. Mean age of all patients was years. The LR and MR was 14.3% and 8.3%, respectively, in patients undergoing first resection, whereas it was 21.4% and 13.7%, respectively, in patients undergoing revision surgery. Average duration from previous unplanned excision was 8 months. Twelve patients were referred immediately after excised specimen revealed STS, while 39 patients presented after evident local recurrence. Wide reexcision was attempted in 48 patients while three patients need amputation. Adjuvant radiotherapy was administered in all patients undergoing limb-sparing surgery. Ten patients needed adjuvant chemotherapy. We conclude that wide reexcision of STS has poorer outcomes compared to planned excision. Therefore, patients with soft tissue masses should be managed by multidisciplinary oncology team at specialized cancer centers. Hafiz Muhammad Umer, Masood Umer, Irfan Qadir, Nadeem Abbasi, and Nehal Masood Copyright © 2013 Hafiz Muhammad Umer et al. All rights reserved. Thu, 18 Apr 2013 17:26:26 +0000 http://www.hindawi.com/journals/srcm/2013/679323/ Background. One-third of all extremity soft tissue sarcomas are misdiagnosed and inappropriately excised without proper preoperative diagnosis and planning. This study aimed at examining the clinical judgment of residents in both general and orthopaedic surgery and at determining whether resident education plays a role in appropriately managing unknown soft tissue masses. Methods. A case-based survey was used to assess clinical decisions, practice patterns, and demographics. Aggregate response for all of the clinical cases by each respondent was correlated with the selections made for practice patterns and demographic data. Results. A total of 381 responses were returned. A higher percentage of respondents from the orthopaedic group (84.2%) noted having a dedicated STS rotation as compared to the general surgery group (35.8%) . Depth, size, and location of the mass, rate of growth, and imaging characteristics were considered to be important factors. Each additional year of training resulted in 10% increased odds of selecting the correct clinical decision for both groups. Conclusion. Our study showed that current residents in both orthopaedic surgery and general surgery are able to appropriately identify patients with suspicious masses. Continuing education in sarcoma care should be implemented beyond the years of residency training. Vignesh K. Alamanda, Samuel N. Crosby, Shannon L. Mathis, Kristin R. Archer, Kyla P. Terhune, and Ginger E. Holt Copyright © 2013 Vignesh K. Alamanda et al. All rights reserved. Tue, 16 Apr 2013 13:02:10 +0000 http://www.hindawi.com/journals/srcm/2013/205832/ This paper deals with bilateral vascularized fibular grafts (BVFG) as a method for reconstruction of metadiaphyseal defects of the femur and tibia in young patients suffering from malignant bone tumors of the lower limb. This reconstructional technique was used in 11 patients undergoing metadiaphyseal resection of lower limb malignant bone tumors. All patients with Ewing’s sarcoma and osteosarcoma had multimodal treatment according to the EURO-E.W.I.N.G 99 or COSS-96 protocol. Median FU was 63 months. None of the patients experienced local recurrence during FU. 2 patients died due to distant disease during FU. Full weight- bearing was permitted after a mean of 8 months. The median MSTS score was 87%. Complications occurred in five patients. None of the complications led to failure of the biological reconstruction or to amputation. Biological reconstruction of osseous defects is always desirable when possible and aims at a permanent solution. Good functional and durable results can be obtained by using BVFG for the reconstruction of metadiaphyseal defects of the femur and tibia. Radiotherapy in the multimodal setting increases the risk for graft or fixation failure. Maya Niethard, Carmen Tiedke, Dimosthenis Andreou, Frank Traub, Mario Kuhnert, Mathias Werner, and Per-Ulf Tunn Copyright © 2013 Maya Niethard et al. All rights reserved. Tue, 09 Apr 2013 13:42:26 +0000 http://www.hindawi.com/journals/srcm/2013/524395/ Structural bone allograft has been used in bone defect reconstruction during the last fifty years with acceptable results. However, allograft selection methods were based on 2-dimensional templates using X-rays. Thanks to preoperative planning platforms, three-dimensional (3D) CT-derived bone models were used to define size and shape comparison between host and donor. The purpose of this study was to describe the workflow of this virtual technique in order to explain how to choose the best allograft using a virtual bone bank system. We measured all bones in a 3D virtual environment determining the best match. The use of a virtual bone bank system has allowed optimizing the allograft selection in a bone bank, providing more information to the surgeons before surgery. In conclusion, 3D preoperative planning in a virtual environment for allograft selection is an important and helpful tool in order to achieve a good match between host and donor. Lucas Eduardo Ritacco, German Luis Farfalli, Federico Edgardo Milano, Miguel Angel Ayerza, Domingo Luis Muscolo, and Luis Aponte-Tinao Copyright © 2013 Lucas Eduardo Ritacco et al. All rights reserved. Wed, 03 Apr 2013 15:41:33 +0000 http://www.hindawi.com/journals/srcm/2013/745360/ Background. Surgical treatment of malignant pelvic bone tumors can be very challenging. The objective of this retrospective study was to evaluate the oncological as well as the clinical and functional outcome after limb salvage surgery and biological reconstruction. Methods. The files of 27 patients with malignant pelvic bone tumors, who underwent surgical resection at our department between 2000 and 2011, were retrospectively analyzed (9 Ewing's sarcoma, 8 chondrosarcoma, 4 osteosarcoma, 1 synovial sarcoma, 1 malignant fibrous histiocytoma, and 4 carcinoma metastases). Results. After internal hemipelvectomy reconstruction was performed by hip transposition (), using autologous nonvascularised fibular graft () or autologous iliac crest bone graft (). In one patient a proximal femor prothetis and in three patients a total hip prosthesis was implanted at the time of resection. The median follow-up was 33 months. Two- and five-year disease-specific survival rates of all patients were 86.1% and 57.7%, respectively. The mean functional MSTS score was 16.5 (~55%) for all patients. Conclusion. On the basis of the oncological as well as the clinical and functional outcome, biological reconstruction after internal hemipelvectomy seems to be a reliable technique for treating patients with a malignant pelvic bone tumor. Frank Traub, Dimosthenis Andreou, Maya Niethard, Carmen Tiedke, Mathias Werner, and Per-Ulf Tunn Copyright © 2013 Frank Traub et al. All rights reserved. Wed, 03 Apr 2013 11:33:52 +0000 http://www.hindawi.com/journals/srcm/2013/318767/ Reconstruction of the distal radius following tumour resection is challenging and various techniques are recorded. We retrospectively analysed the outcome of five patients (one male and four females) after reconstruction of the distal radius with osteoarticular allograft, following tumour resection. Mean followup was 32 months (range, 4–121). In three of the five patients the dominant limb was affected. Mean bone resection length was 6.5 centimetres (range, 5–11.5). Two grafts developed nonunion, both successfully treated with autologous bone grafting. No infection, graft fracture, or failure occurred. Mean flexion/extension was 38/60 degrees and mean pronation/supination was 77/77 degrees. The mean Mayo wrist score was 84 and the mean DASH score was 8, both representing a good functional result. Therefore we state the notion that osteoarticular allograft reconstruction of distal radius provides good to excellent functional results. Katharina Rabitsch, Werner Maurer-Ertl, Ulrike Pirker-Frühauf, Thomas Lovse, Reinhard Windhager, and Andreas Leithner Copyright © 2013 Katharina Rabitsch et al. All rights reserved. Mon, 25 Mar 2013 16:15:54 +0000 http://www.hindawi.com/journals/srcm/2013/505321/ Introduction. Peripheral de-differentiated chondrosarcomas are among the rarest malignant mesenchymal tumors. This tumor’s descriptive radiographic characteristics are reported but objective quantification does not exist. This investigation surveyed imaging of peripheral de-differentiated chondrosarcomas to facilitate better recognition of these uncommon tumors. Methods. Database interrogation for peripheral de-differentiated chondrosarcomas was performed; 23 patients were identified and imaging for 18 was reviewed. A musculoskeletal radiologist reviewed all studies for mineralization characteristics; presence of pre-existing osteochondromas; preserved corticomedullary continuity; adjacent cortical obliteration; soft-tissue mass; tumor necrosis; and presence of a cartilage cap. Tumor luminance was measured with computer software. Results. Mineralization was present in 17 tumors. Pre-existing exostoses were evident in nine cases, corticomedullary continuity was preserved in three cases. There was no difference in mineralization or other characteristics based on tumor location. Mean tumor luminance was 94.9 candela/m2. Conclusions. The imaging characteristics described for central de-differentiated chondrosarcomas are similar to the peripheral form of this tumor. Peripheral mineralization with a bimorphic pattern on CT scan and the presence of a soft-tissue mass should be considered worrisome for a peripheral de-differentiated chondrosarcoma, particularly in the setting of multiple hereditary exostoses. Eric R. Henderson, Elisa Pala, Andrea Angelini, Eugenio Rimondi, and Pietro Ruggieri Copyright © 2013 Eric R. Henderson et al. All rights reserved. Wed, 20 Mar 2013 13:29:36 +0000 http://www.hindawi.com/journals/srcm/2013/767960/ We analyze the delay in diagnosis and tumor size of malignant bone tumors of the foot in a retrospective study. We compared the oncological and surgical long-term results with identical tumor at other anatomical sites in order to analyze the biological behavior of sarcomas that are found in the foot. Thirty-two patients with a histologically proven malignant bone tumor (fifteen chondrosarcomas, nine osteosarcomas, and eight Ewing sarcomas) between the years 1969 and 2008 were included. The median follow-up was 11.9 years. The overall median time gap between the beginning of symptoms and diagnosis in the study group was 10 months. Ewing sarcoma presented with the longest delay in diagnosis (median of 18 months), followed by osteosarcoma (median of 15 months) and chondrosarcoma (median of 7.5 months). The delay in diagnosis of these tumors was significantly longer than that of equivalent tumors at other skeletal sites, but the 5- and 10-year survival rates and the occurrence of distant metastases were comparable. In contrast, the average size of foot tumors was 5- to 30-fold less than that of tumors analyzed at other skeletal sites. This study indicates that sarcomas of the foot demonstrate a distinct biological behavior compared to the same tumor types at other skeletal sites. M. Brotzmann, F. Hefti, D. Baumhoer, and A. H. Krieg Copyright © 2013 M. Brotzmann et al. All rights reserved. Sun, 17 Mar 2013 15:40:59 +0000 http://www.hindawi.com/journals/srcm/2013/863056/ Soft tissue sarcomas are a rare type of cancer generally treated with palliative chemotherapy when in the advanced stage. There is a lack of published health utility data for locally advanced “inoperable”/metastatic disease (ASTS), essential for calculating the cost-effectiveness of current and future treatments. This study estimated time trade-off (TTO) and standard gamble (SG) preference values associated with four ASTS health states (progressive disease, stable disease, partial response, complete response) among members of the general public in the UK (). The four health states were associated with decreases in preference values from full health. Complete response was the most preferred health state (mean utility of 0.60 using TTO). The second most preferred health state was partial response followed by stable disease (mean utilities were 0.51 and 0.43, respectively, using TTO). The least preferred health state was progressive disease (mean utility of 0.30 using TTO). The utility value for each state was significantly different from one another (). This study demonstrated and quantified the impact that different treatment responses may have on the health-related quality of life of patients with ASTS. Julian F. Guest, Erikas Sladkevicius, Nicholas Gough, Mark Linch, and Robert Grimer Copyright © 2013 Julian F. Guest et al. All rights reserved. Mon, 11 Mar 2013 08:41:11 +0000 http://www.hindawi.com/journals/srcm/2013/168145/ Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma. Methods. A Simon two-stage phase II design was used to determine if there was sufficient activity to pursue further. The primary endpoint was tumor response rate by RECIST 1.0. Patients were treated with ipilimumab 3 mg/kg intravenously every 3 weeks for three cycles and then restaged. Retreatment was possible for patients receiving an extra three-week break from therapy. Sera and peripheral blood mononuclear cells were collected before and during therapy to assess NY-ESO-1-specific immunity. Results. Six patients were enrolled and received 1–3 cycles of ipilimumab. All patients showed clinical or radiological evidence of disease progression after no more than three cycles of therapy, for a RECIST response rate of 0%. The study was stopped for slow accrual, lack of activity, and lack of immune response. There was no evidence of clinically significant either serologic or delayed type hypersensitivity responses to NY-ESO-1 before or after therapy. Conclusion. Despite high expression of CT antigens by synovial sarcomas of patients treated in this study, there was neither clinical benefit nor evidence of anti-CT antigen serological responses. Assessment of the ability of synovial sarcoma cell lines to present cancer-germ cell antigens may be useful in determining the reason for the observed lack of immunological or clinical activity. Robert G. Maki, Achim A. Jungbluth, Sacha Gnjatic, Gary K. Schwartz, David R. D’Adamo, Mary Louise Keohan, Michael J. Wagner, Kelly Scheu, Rita Chiu, Erika Ritter, Jennifer Kachel, Israel Lowy, Lloyd J. Old, and Gerd Ritter Copyright © 2013 Robert G. Maki et al. All rights reserved. Wed, 06 Mar 2013 14:31:26 +0000 http://www.hindawi.com/journals/srcm/2013/757915/ Caroline Oudot, Daniel Orbach, Véronique Minard-Colin, Jean Michon, Pierre Mary, Christophe Glorion, Sylvie Helfre, Jean-Louis Habrand, and Odile Oberlin Copyright © 2013 Caroline Oudot et al. All rights reserved. Mon, 04 Mar 2013 13:46:50 +0000 http://www.hindawi.com/journals/srcm/2013/787653/ To achieve local control of malignant pediatric bone tumors and to provide satisfactory oncological results, adequate resection margins are mandatory. The local recurrence rate is directly related to inappropriate excision margins. The present study describes a method for decreasing the resection margin width and ensuring that the margins are adequate. This method was developed in the tibia, which is a common site for the most frequent primary bone sarcomas in children. Magnetic resonance imaging (MRI) and computerized tomography (CT) were used for preoperative planning to define the cutting planes for the tumors: each tumor was segmented on MRI, and the volume of the tumor was coregistered with CT. After preoperative planning, a surgical guide (patient-specific instrument) that was fitted to a unique position on the tibia was manufactured by rapid prototyping. A second instrument was manufactured to adjust the bone allograft to fit the resection gap accurately. Pathologic evaluation of the resected specimens showed tumor-free resection margins in all four cases. The technologies described in this paper may improve the surgical accuracy and patient safety in surgical oncology. In addition, these techniques may decrease operating time and allow for reconstruction with a well-matched allograft to obtain stable osteosynthesis. Laura Bellanova, Laurent Paul, and Pierre-Louis Docquier Copyright © 2013 Laura Bellanova et al. All rights reserved. Thu, 28 Feb 2013 11:40:56 +0000 http://www.hindawi.com/journals/srcm/2013/608964/ Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat) over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity. Jason E. Cain, Andrew McCaw, W. Samantha N. Jayasekara, Fernando J. Rossello, Kieren D. Marini, Aaron T. Irving, Maya Kansara, David M. Thomas, David M. Ashley, and D. Neil Watkins Copyright © 2013 Jason E. Cain et al. All rights reserved. Thu, 14 Feb 2013 17:57:21 +0000 http://www.hindawi.com/journals/srcm/2013/925413/ In comparison with the lower extremity, there is relatively paucity literature reporting survival and clinical results of allograft reconstructions after excision of a bone tumor of the upper extremity. We analyze the survival of allograft reconstructions in the upper extremity and analyze the final functional score according to anatomical site and type of reconstruction. A consecutive series of 70 allograft reconstruction in the upper limb with a mean followup of 5 years was analyzed, 38 osteoarticular allografts, 24 allograft-prosthetic composites, and 8 intercalary allografts. Kaplan-Meier survival analysis of the allografts was performed, with implant revision for any cause and amputation used as the end points. The function evaluation was performed using MSTS functional score. Sixteen patients (23%) had revision surgery for 5 factures, 2 infections, 5 allograft resorptions, and 2 local recurrences. Allograft survival at five years was 79% and 69% at ten years. In the group of patients treated with an osteoarticular allograft the articular surface survival was 90% at five years and 54% at ten years. The limb salvage rate was 98% at five and 10 years. We conclude that articular deterioration and fracture were the most frequent mode of failure in proximal humeral osteoarticular reconstructions and allograft resorption in elbow reconstructions. The best functional score was observed in the intercalary humeral allograft. Luis A. Aponte-Tinao, Miguel A. Ayerza, D. Luis Muscolo, and German L. Farfalli Copyright © 2013 Luis A. Aponte-Tinao et al. All rights reserved. Thu, 14 Feb 2013 14:58:48 +0000 http://www.hindawi.com/journals/srcm/2013/480713/ Osteosarcoma (OS) is the most common primary malignancy of bone. Mortality is determined by the presence of metastatic disease, but little is known regarding the biochemical events that drive metastases. Two murine OS cell lines, K7M2 and K12, are related but differ significantly in their metastatic potentials: K7M2 is highly metastatic whereas K12 displays much less metastatic potential. Using this experimental system, the mammalian target of rapamycin (mTOR) pathway has been implicated in OS metastasis. We also discovered that aldehyde dehydrogenase (ALDH, a stem cell marker) activity is higher in K7M2 cells than K12 cells. Rapamycin treatment reduces the expression and enzymatic activity of ALDH in K7M2 cells. ALDH inhibition renders these cells more susceptible to apoptotic death when exposed to oxidative stress. Furthermore, rapamycin treatment reduces bone morphogenetic protein-2 (BMP2) and vascular endothelial growth factor (VEGF) gene expression and inhibits K7M2 proliferation, migration, and invasion in vitro. Inhibition of ALDH with disulfiram correlated with decreased mTOR expression and activity. In conclusion, we provide evidence for interaction between mTOR activity, ALDH activity, and metastatic potential in murine OS cells. Our work suggests that mTOR and ALDH are therapeutic targets for the treatment and prevention of OS metastasis. Xiaodong Mu, Christian Isaac, Trevor Schott, Johnny Huard, and Kurt Weiss Copyright © 2013 Xiaodong Mu et al. All rights reserved. Thu, 14 Feb 2013 09:12:03 +0000 http://www.hindawi.com/journals/srcm/2013/489652/ Allograft-prosthesis composite (APC) can restore capsular and ligamentous tissues of the knee sacrificed in a tumor extirpation. We asked if performing APC would restore knee stability and allow the use of nonconstrained arthroplasty while preventing aseptic loosening. We retrospectively compared 50 knee APCs performed with non-constrained revision knee prosthesis (Group 1) with 36 matched APCs performed with a constrained prosthesis (Group 2). In Group 1, the survival rate was 69% at five and 62% at ten years. Sixteen reconstructions were removed due to complications: eight deep infections, three fractures, two instabilities, one aseptic loosening, one local recurrence, and one nonunion. In Group 2, the survival rate was 80% at five and 53% at ten years. Nine reconstructions were removed: 3 due to deep infections, 3 to fractures, and 3 to aseptic loosening. In both groups, we observed more allograft fractures when the prosthetic stem does not bypass the host-donor osteotomy (). Both groups had mainly good or excellent MSTS functional results. Survival rate and functional scores and aseptic loosening were similar in both groups. A rotating-hinge APC is recommended when host-donor soft tissue reconstruction fails to restore knee instability. The use of a short prosthetic stem has a statistical relationship with APC fractures. German L. Farfalli, Luis A. Aponte-Tinao, Miguel A. Ayerza, D. Luis Muscolo, Patrick J. Boland, Carol D. Morris, Edward A. Athanasian, and John H. Healey Copyright © 2013 German L. Farfalli et al. All rights reserved. Sun, 10 Feb 2013 16:17:33 +0000 http://www.hindawi.com/journals/srcm/2013/147541/ Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/β-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Using in vivo and in vitro studies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector. In vitro experiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy. Carol H. Lin, Yi Guo, Samia Ghaffar, Peter McQueen, Jonathan Pourmorady, Alexander Christ, Kevin Rooney, Tao Ji, Ramez Eskander, Xiaolin Zi, and Bang H. Hoang Copyright © 2013 Carol H. Lin et al. All rights reserved. Sun, 03 Feb 2013 11:24:01 +0000 http://www.hindawi.com/journals/srcm/2013/315170/ Purpose. Malignant rhabdoid tumor (MRT) is an uncommon tumor that rarely occurs outside of renal and central nervous system (CNS) sites. Data from the literature were compiled to determine prognostic factors, including both demographic and treatment variables of malignant rhabdoid tumor, focusing on those tumors arising in extra-renal, extra-CNS (ER/EC MRT) sites. Patients and Methods. A systematic review and meta-analysis was performed by extracting demographic, treatment, and survival follow up on 167 cases of primary ER/EC MRT identified in the literature. Results. No survival differences were observed between those treated with or without radiation, or with or without chemotherapy. A Cox regression of overall survival revealed several independent prognostic factors. Surgical excision had a 74% (P = 0.0003) improvement in survival. Actinomycin had a 73% (P = 0.093) improvement in survival. Older age was associated with improved survival. The four-year survival, by Kaplan-Meier estimates, comparing patients less than two years old versus older than two at diagnosis was 11% versus 35%, respectively (P = 0.0001, Log-Rank). Conclusion. ER/EC MRT is a rare, soft-tissue tumor with a poor prognosis most commonly occurring in children. Surgical resection, treatment with actinomycin, and older age at diagnosis are all associated with improved survival. Ryan Horazdovsky, J. Carlos Manivel, and Edward Y. Cheng Copyright © 2013 Ryan Horazdovsky et al. All rights reserved. Mon, 28 Jan 2013 13:41:09 +0000 http://www.hindawi.com/journals/srcm/2013/450478/ The insulin-like growth factor 1 receptor (IGF-1R) has been considered an important therapeutic target in Ewing sarcoma (ES), generating a need to identify the subset of patients most likely to respond to IGF-1R inhibitors. We assessed IGF-1R expression in ES cell lines and patient tumors to understand the variable clinical responses to anti-IGF-1R therapy. Using ligand-binding displacement, we measured between 13,000 and 40,000 receptors per cell in ES cell lines. We used ELISA to quantify IGF-1R in patient tumors, which expressed 4.8%  ± 3.7 to 20.0%  ± 0.2 of the levels in a positive control cell line overexpressing IGF-1R. Flow cytometry showed markedly reduced IGF-1R expression in ES cell lines compared to a standard positive control cell line. The IGF1R gene was sequenced in 47 ES tumor samples and 8 ES cell lines; only one tumor sample showed a nonsynonymous mutation, R1353H, in a region with low functional impact. Finally, we assessed IGF-1R pathway activity in the ES stem cell (ESSC) population, to characterize its potential for resistance to anti-IGF-1R therapy, using Luminex technology. We found no significant differences in IGF-1R pathway activity between ESSCs and the total cell population. Overall, our findings suggest that IGF-1R as a therapeutic target in this sarcoma may require reevaluation. Alison O'Neill, Nilay Shah, Naamah Zitomersky, Marc Ladanyi, Neerav Shukla, Aykut Üren, David Loeb, and Jeffrey Toretsky Copyright © 2013 Alison O'Neill et al. All rights reserved. Tue, 15 Jan 2013 15:30:53 +0000 http://www.hindawi.com/journals/srcm/2013/485483/ Background and Objectives. Atypical lipomas are uncommon, slow-growing benign tumors. While surgery has been the primary treatment modality, we have managed some patients with radiation (RT) as a component of the treatment and have reported their outcomes in this study. Methods. A retrospective review of all cases of extremity and trunk atypical lipomas in The Sarcoma Database at the study institution was conducted. Results. Thirteen patients were identified. All patients underwent surgical resection at initial presentation and received pre- or postoperative radiation for subtotal resection (), local recurrence (), or progressive disease (). The median total radiation dose was 50 Gy. Median followup was 65.1 months. All patients treated with RT remained free of disease at the last followup. No grade 3 or higher late toxicity from radiation was observed. No cases of tumor dedifferentiation occurred. Conclusion. For recurrent or residual atypical lipomas, a combination of reexcision and RT can provide long-term local control with acceptable morbidity. For recurrent tumors, pre-op RT of 50 Gy appears to be an effective and well-tolerated management approach. Josephine Kang, Maikel Botros, Saveli Goldberg, Christine Giraud, G. Petur Nielsen, Yen-Lin Chen, Kevin Raskin, Joseph Schwab, Sam S. Yoon, Francis J. Hornicek, and Thomas F. DeLaney Copyright © 2013 Josephine Kang et al. All rights reserved. Mon, 14 Jan 2013 08:47:08 +0000 http://www.hindawi.com/journals/srcm/2013/153640/ Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology. Boris Michael Holzapfel, Mohit Prashant Chhaya, Ferry Petrus Wilhelmus Melchels, Nina Pauline Holzapfel, Peter Michael Prodinger, Ruediger von Eisenhart-Rothe, Martijn van Griensven, Jan-Thorsten Schantz, Maximilian Rudert, and Dietmar Werner Hutmacher Copyright © 2013 Boris Michael Holzapfel et al. All rights reserved. Mon, 31 Dec 2012 14:46:30 +0000 http://www.hindawi.com/journals/srcm/2012/439208/ Peter Choong Copyright © 2012 Peter Choong. All rights reserved. Tue, 18 Dec 2012 13:51:20 +0000 http://www.hindawi.com/journals/srcm/2012/197540/ Bulk allograft reconstruction plays an important role in limb-salvage surgery; however, non-union has been reported in up to 27% of cases. The purpose of this study is to quantify average surface contact areas across simulated intraoperative osteotomies using both free-hand and computer-assisted navigation techniques. Pressure-sensitive paper was positioned between two cut ends of a validated composite sawbone and compression was applied using an eight-hole large fragment dynamic compression plate. Thirty-two samples were analyzed for surface area contact to determine osteotomy congruity. Mean contact area using the free-hand osteotomy technique was equal to 0.21 square inches. Compared with a control of 0.69 square inches, average contact area was found to be 30.5% of optimal surface contact. Mean contact area using computer-assisted navigation was equal to 0.33 square inches. Compared with a control of 0.76 square inches, average contact area was found to be 43.7% of optimal surface contact. Limited contact achieved using standard techniques may play a role in the high rate of observed non-union, and an increase in contact area using computer-assisted navigation may improve rates of bone healing. The development of an oncology software package and navigation hardware may serve an important role in decreasing non-union rates in limb salvage surgery. Ajay Lall, Eric Hohn, Mimi Y. Kim, Richard G. Gorlick, John A. Abraham, and David S. Geller Copyright © 2012 Ajay Lall et al. All rights reserved. Tue, 18 Dec 2012 08:01:59 +0000 http://www.hindawi.com/journals/srcm/2012/620834/ The genetic mechanisms involved in the transformation from a benign neurofibroma to a malignant sarcoma in patients with neurofibromatosis-type-1- (NF1-)associated or sporadic malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. It is hypothesized that many genetic changes are involved in transformation. Recently, it has been shown that both phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) play important roles in the initiation of peripheral nerve sheath tumors (PNSTs). In human MPNSTs, PTEN expression is often reduced, while EGFR expression is often induced. We tested if these two genes cooperate in the evolution of PNSTs. Transgenic mice were generated carrying conditional floxed alleles of Pten, and EGFR was expressed under the control of the 2′,3′-cyclic nucleotide 3′phosphodiesterase (Cnp) promoter and a desert hedgehog (Dhh) regulatory element driving Cre recombinase transgenic mice (Dhh-Cre). Complete loss of Pten and EGFR overexpression in Schwann cells led to the development of high-grade PNSTs. In vitro experiments using immortalized human Schwann cells demonstrated that loss of PTEN and overexpression of EGFR cooperate to increase cellular proliferation and anchorage-independent colony formation. This mouse model can rapidly recapitulate PNST onset and progression to high-grade PNSTs, as seen in sporadic MPNST patients. Vincent W. Keng, Adrienne L. Watson, Eric P. Rahrmann, Hua Li, Barbara R. Tschida, Branden S. Moriarity, Kwangmin Choi, Tilat A. Rizvi, Margaret H. Collins, Margaret R. Wallace, Nancy Ratner, and David A. Largaespada Copyright © 2012 Vincent W. Keng et al. All rights reserved. Sun, 02 Dec 2012 14:59:50 +0000 http://www.hindawi.com/journals/srcm/2012/960194/ Soft-tissue sarcomas spread predominantly to the lung and it is unclear how often FDG-PET scans will detect metastases not already obvious by chest CT scan or clinical examination. Adult limb and body wall soft-tissue sarcoma cases were identified retrospectively. Ewing’s sarcoma, rhabdomyosarcoma, GIST, desmoid tumors, visceral tumors, bone tumors, and retroperitoneal sarcomas were excluded as were patients imaged for followup, response assessment, or recurrence. All patients had a diagnostic chest CT scan. 109 patients met these criteria, 87% of which had intermediate or high-grade tumors. The most common pathological diagnoses were leiomyosarcoma (17%), liposarcoma (17%), and undifferentiated or pleomorphic sarcoma (16%). 98% of previously unresected primary tumors were FDG avid. PET scans were negative for distant disease in 91/109 cases. The negative predictive value was 89%. Fourteen PET scans were positive. Of these, 6 patients were already known to have metastases, 3 were false positives, and 5 represented new findings of metastasis (positive predictive value 79%). In total, 5 patients were upstaged by FDG-PET (4.5%). Although PET scans may be of use in specific circumstances, routine use of FDG PET imaging as part of the initial staging of soft-tissue sarcomas was unlikely to alter management in our series. David Roberge, Siavosh Vakilian, Yazan Z. Alabed, Robert E. Turcotte, Carolyn R. Freeman, and Marc Hickeson Copyright © 2012 David Roberge et al. All rights reserved. Tue, 27 Nov 2012 13:09:47 +0000 http://www.hindawi.com/journals/srcm/2012/301975/ Primary malignant bone tumours, osteosarcomas, and Ewing sarcomas are rare diseases which occur mainly in adolescents and young adults. With the current therapies, some patients remain very difficult to treat, such as tumour with poor histological response to preoperative CT (or large initial tumour volume for Ewing sarcomas not operated), patients with multiple metastases at or those who relapsed. In order to develop new therapies against these rare tumours, we need to unveil the key driving factors and molecular abnormalities behind the malignant characteristics and to broaden our understanding of the phenomena sustaining the metastatic phenotype and treatment resistance in these tumours. In this paper, starting with the biology of these tumours, we will discuss potential therapeutic targets aimed at increasing local tumour control, limiting metastatic spread, and finally improving patient survival. Nathalie Gaspar, Angela Di Giannatale, Birgit Geoerger, Françoise Redini, Nadège Corradini, Natacha Enz-Werle, Franck Tirode, Perrine Marec-Berard, Jean-Claude Gentet, Valérie Laurence, Sophie Piperno-Neumann, Odile Oberlin, and Laurence Brugieres Copyright © 2012 Nathalie Gaspar et al. All rights reserved. Sun, 25 Nov 2012 14:41:14 +0000 http://www.hindawi.com/journals/srcm/2012/636405/ Background. This study was conducted to investigate the clinical characteristics and treatment results of osteosarcoma in pediatric patients during the past 30 years. Trends in survival rates and long-term toxicity were analyzed. Procedure. 130 pediatric patients under the age of 20 years with primary localized or metastatic high-grade osteosarcoma were analyzed regarding demographic, treatment-related variables, long-term toxicity, and survival data. Results. Comparison of the different time periods of treatment showed that the 5-year OS improved from 58.6% for children diagnosed during 1979–1983 to 78.6% for those diagnosed during 2003–2008 (). Interestingly, the basic treatment agents including cisplatin, doxorubicin, and methotrexate remained the same. Treatment reduction due to acute toxicity was less frequent in patients treated in the last era (7.1% versus 24.1% in patients treated in 1979–1983; ). Furthermore, late cardiac effects and secondary malignancies can become evident many years after treatment. Conclusion. We elucidate the prevalence of toxicity to therapy of patients with osteosarcoma over the past 30 years. The overall improvement in survival may in part be attributed to improved supportive care allowing regimens to be administered to best advantage with higher tolerance of chemotherapy and therefore less chemotherapy-related toxicity. Melanie M. Hagleitner, Eveline S. J. M. de Bont, and D. Maroeska W. M. te Loo Copyright © 2012 Melanie M. Hagleitner et al. All rights reserved. Wed, 21 Nov 2012 08:36:22 +0000 http://www.hindawi.com/journals/srcm/2012/425636/ Osteosarcomas are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. Global protein expression studies, namely, proteomic studies, can offer important clues to understanding the tumor biology that cannot be obtained by other approaches. These studies, such as two-dimensional gel electrophoresis and mass spectrometry, have provided protein expression profiles of osteosarcoma that can be used to develop novel diagnostic and therapeutic biomarkers, as well as to understand biology of tumor progression and malignancy. In this paper, a brief description of the methodology will be provided followed by a few examples of the recent proteomic studies that have generated new information regarding osteosarcomas. Yoshiyuki Suehara, Daisuke Kubota, Kazutaka Kikuta, Kazuo Kaneko, Akira Kawai, and Tadashi Kondo Copyright © 2012 Yoshiyuki Suehara et al. All rights reserved. Tue, 13 Nov 2012 08:38:56 +0000 http://www.hindawi.com/journals/srcm/2012/937506/ Osteosarcoma (OS) is a rare bone neoplasm that affects mainly adolescents. It is associated with poor prognosis in case of metastases formation. The search for metastasis predicting markers is therefore imperative to optimize treatment strategies for patients at risk and important for the search of new drugs for the treatment of this devastating disease. Here, we have analyzed by microarray the differential gene expression in four human and two mouse OS cell line systems consisting of parental cell lines with low metastatic potential and derivatives thereof with increased metastatic potential. Using two osteoblastic cell line systems, the most common OS phenotype, we have identified forty-eight common genes that are differentially expressed in metastatic cell lines compared to parental cells. The identified subset of metastasis relevant genes in osteoblastic OS overlapped only minimally with differentially expressed genes in the other four preosteoblast or nonosteoblastic cell line systems. The results imply an OS phenotype specific expression pattern of metastasis regulating proteins and form a basis for further investigation of gene expression profiles in patients’ samples combined with survival analysis with the aim to optimize treatment strategies to develop new drugs and to consequently improve the survival of patients with the most common form of osteoblastic OS. Roman Muff, Ram Mohan Ram Kumar, Sander M. Botter, Walter Born, and Bruno Fuchs Copyright © 2012 Roman Muff et al. All rights reserved. Thu, 18 Oct 2012 10:35:34 +0000 http://www.hindawi.com/journals/srcm/2012/164803/ Although osteosarcoma is the most common primary malignant bone tumor in children and adolescents, its cell of origin and the genetic alterations are unclear. Previous studies have shown that serially introducing hTERT, SV40 large TAg, and H-Ras transforms human mesenchymal stem cells into two distinct sarcomas cell populations, but they do not form osteoid. In this study, β-catenin was introduced into mesenchymal stem cells already containing hTERT and SV40 large TAg to analyze if this resulted in a model which more closely recapitulated osteosarcoma. Results. Regardless of the level of induced β-catenin expression in the stable transfectants, there were no marked differences induced in their phenotype or invasion and migration capacity. Perhaps more importantly, none of them formed tumors when injected into immunocompromised mice. Moreover, the resulting transformed cells could be induced to osteogenic and chondrogenic differentiation but not to adipogenic differentiation. Conclusions. β-catenin, although fostering osteogenic differentiation, does not induce the malignant features and tumorigenicity conveyed by oncogenic H-RAS when introduced into partly transformed mesenchymal stem cells. This may have implications for the role of β-catenin in osteosarcoma pathogenesis. It also may suggest that adipogenesis is an earlier branch point than osteogenesis and chondrogenesis in normal mesenchymal differentiation. Sajida Piperdi, Lukas Austin-Page, David Geller, Manpreet Ahluwalia, Sarah Gorlick, Jonathan Gill, Amy Park, Wendong Zhang, Nan Li, So Hak Chung, and Richard Gorlick Copyright © 2012 Sajida Piperdi et al. All rights reserved.