Osteochondromas are benign chondrogenic lesions arising on the external surface of the bone with aberrant cartilage (exostosis) from the perichondral ring that may contain a marrow cavity also. In a few cases, depending on the anatomical site affected, different degrees of edema, redness, paresthesia, or paresis can take place due to simple contact or friction. Also, depending on their closeness to neurovascular structures, the procedure of excision becomes crucial to avoid recurrence. We report a unique case of recurrent osteochondroma of the proximal humerus enclosing the brachial artery which makes for an important case and procedure to ensure that no relapse occurs. We report a unique case of a 13-year-old female who had presented with a history of pain and recurrent swelling for 5 years. The swelling size was 4.4 cm x 3.7 cm x 4 cm with a previous history of swelling at the same site operated in 2018. CT reports were suggestive of a large well defined broad-based exophytic diaphyseal lesion in the medial side of the proximal humerus extending posteriorly. Another similar morphological lesion measuring approximately 9 mm x 7 mm was noted involving the posterior humeral shaft. The minimal distance between the lesion and the brachial artery was 2 mm just anterior to the posterio-medial growth. Two intervals were made, first between the tumor and the neurovascular bundle and the other between the anterior tumor and brachial artery followed by exostosis and cauterization of the base. Proper curettage and excision of the tumor was done after dissecting and removing the soft tissue, blood vessels, and nerves so that there were very less chances of relapse. Post-operative X-ray was done and post 6 months of follow-up, there were no changes, and no relapse was observed. Thus, when presented with a case of recurrent osteochondroma of the proximal humerus, osteochondroma could also be in proximity to important vasculature as in this case enclosing the brachial artery. Thus, proper curettage and excision should be done in such cases to avoid recurrence

Decreasing the chance of local relapse or infection after surgical excision of bone metastases is a main goals in orthopedic oncology. Indeed, bone metastases have high incidence rate (up to 75%) and important cross-relations with infection and bone regeneration. Even in patients with advanced cancer, bone gaps resulting from tumor excision must be filled with bone substitutes. Functionalization of these substitutes with antitumor and antibacterial compounds could constitute a promising approach to overcome infection and tumor at one same time. Here, for the first time, we propose the use of nanostructured zinc-bone apatite coatings having antitumor and antimicrobial efficacy. The coatings are obtained by Ionized Jet Deposition from composite targets of zinc and bovine-derived bone apatite. Antibacterial and antibiofilm efficacy of the coatings is demonstrated in vitro against S. Aureus and E. Coli. Anti-tumor efficacy is investigated against MDA- MB-231 cells and biocompatibility is assessed on L929 and MSCs. A microfluidic based approach is used to select the optimal concentration of zinc to be used to obtain antitumor efficacy and avoid cytotoxicity, exploiting a custom gradient generator microfluidic device, specifically designed for the experiments. Then, coatings capable of releasing the desired amount of active compounds are manufactured. Films morphology, composition and ion-release are studies by FEG- SEM/EDS, XRD and ICP. Efficacy and biocompatibility of the coatings are verified by investigating MDA, MSCs and L929 viability and morphology by Alamar Blue, Live/Dead Assay and FEG-SEM at different timepoints. Statistical analysis is performed by SPSS/PC + Statistics TM 25.0 software, one-way ANOVA and post-hoc Sheffe? test. Data are reported as Mean ± standard Deviation at a significance level of p <0.05. Results and Discussion. Coatings have a nanostructured surface morphology and a composition mimicking the target. They permit sustained zinc release for over 14 days in medium. Thanks to these characteristics, they show high antibacterial ability (inhibition of bacteria viability and adhesion to substrate) against both the gram + and gram – strain. The gradient generator microfluidic device permits a fine selection of the concentration of zinc to be used, with many potential perspectives for the design of biomaterials. For the first time, we show that zinc and zinc-based coatings have a selective efficacy against MDA cells. Upon mixing with bone apatite, the efficacy is maintained and cytotoxicity is avoided. For the first time, new antibacterial metal-based films are proposed for addressing bone metastases and infection at one same time. At the same time, a new approach is proposed for the design of the coatings, based on a microfluidic approach. We demonstrated the efficacy of Zn against the MDA-MB-231 cells, characterized for their ability to form bone metastases in vivo, and the possibility to use nanostructured metallic coatings against bone tumors. At the same time, we show that the gradient-generator approach is promising for the design of antitumor biomaterials. Efficacy of Zn films must be verified in vivo, but the dual-efficacy coatings appear promising for orthopedic applications

Purpose. Extraskeletal chondrosarcoma is a rare tumor with an indolent course and high propensity for local recurrence and metastasis. This tumor most commonly presents in the proximal extremities of middle-aged males, and is commonly asymptomatic. Although slow growing, these tumors have a significant risk of eventual relapse and metastases, especially to the lung. There are no clinical trials that investigated the best treatment options for this tumor given its very low incidence. The aim of this study is to present the surgical and clinical results of extraskeletal chondrosarcoma, which is a rare tumor. Methods. In our clinic, the information of 13 patients who were diagnosed with extra-skeletal chondrosarcoma between 2006 and 2018 were retrospectively reviewed. Demographic information, tumor size, surgical treatments, chemotherapy and radiotherapy status, follow-up times, recurrence and metastases of the patients were recorded. Results. This study included 13 patients with an average age of 53.6 ± 15 (range, 28 to 73) years diagnosed with extraskelatal chondrosarcoma. In 8 of the patients, the tumor was located in the lower limbs and it was observed that the thigh was located mostly (46.2%). The mean follow-up period of the patients was 52.8 ± 19.9 (range, 24 to 96) months. All patients underwent extensive resection and only one patient had a positive surgical margin. In the follow-up, 5 (38.5%) of the patients developed recurrence, while 6 patients had lung metastasis (46.2%) and 53.8% (7 patients) of the patients exitus. The mean tumor size was 10.4 ± 3.2 (range, 5 to 17) cm. The median survival time of the patients in the study was 61 (50.5–71.4) months. The 5-year survival rate is 51.8%. There was no significant difference between survival times according to age, gender, side, limb location, postoperative RT, recurrence and presence of lung metastasis (log rank tests p > 0.05). The cut off value for exitus obtained by ROC analysis of tumor size was determined as 11 cm (fig 1). Accordingly, the survival time of patients with 11 cm and above tumor size was observed to be statistically significantly shorter. Conclusion. Consequently, ECM is a rare soft tissue sarcoma with high local recurrence and metastasis capacity. Therefore, close follow-up is recommended. The first option should be extensive resection. Studies with large patient series on the prognostic factors of the future ECM are needed. For any figures or tables, please contact the authors directly

In case of spine tumors, when en bloc vertebral column resection (VCR) is indicated and feasible, the segmental defect should be reconstructed in order to obtain an immediate stability and stimulate a solid fusion. The aim of this study is to share our experience on patients who underwent spinal tumor en bloc VCR and reconstruction consecutively. En bloc VCR and reconstruction was performed in 138 patients. Oncological and surgical staging were performed for all patients using Enneking and Weinstein-Boriani-Biagini systems accordingly. Following en bloc VCR of one or more vertebral bodies, a 360° reconstruction was made by applying posterior instrumentation and anterior implant insertion. Modular carbon fiber implants were applied in 111 patients, titanium mesh cage implants in 21 patients and titanium expandable cages in 3 patients; very recently in 3 cases we started to use custom made titanium implants. The latter were prepared according to preoperative planning of en bloc VCR based on CT-scan of the patient, using three dimensional printer. The use of modular carbon fiber implant has not leaded to any mechanical complications in the short and long term follow-up. In addition, due to radiolucent nature of this implant and less artifact production on CT and MRI, tumor relapse may be diagnosed and addressed earlier in compare with other implants, which has a paramount importance in these group of patients. We did not observe any implant failure using titanium cages. However, tumor relapse identification may be delayed due to metal artifacts on imaging modalities. Custom- made implants are economically more affordable and may be a good alternative choice for modular carbon fiber implants. The biocompatibility of the titanium make it a good choice for reconstruction of the defect when combined with bone graft allograft or autograft. Custom made cages theoretically can reproduce patients own biomechanics but should be studied with longer follow-up

Background. The discussion over the duration, type of therapy and regimen to be used in osteoarticular tuberculosis is losing importance in all orthopaedic gathering. Still little consensus is there over the universality of a treatment regime for osteoarticular tuberculosis. Material and Method. 340 new cases of osteoarticular tuberculosis were included in the study that were medically treated in the department of orthopaedics in a tertiary care center between 2001 and 2011. Out of which 202 cases were of spinal tuberculosis and 138 cases of extraspinal tuberculosis. 88 cases of spinal tuberculosis were treated by conventional method and 114 cases by short course chemotherapy. 60 cases of extraarticular tuberculosis were treated by conventional chemotherapy and 78 cases by short course and intermittent therapy. Results. All cases were evaluated on clinical, radiological and haematological basis. Cases who received conventional therapy received 18–24 months of treatment irrespective to the clinical, radiological and haematological parameters. Whereas those who received short course (2HRZE+4 HR) and intermittent therapy (DOTS) were evaluated for clinical improvement. Maximum follow up was of 12.8 years (conventional) minimum follow of 8 years (intermittent). The trend of fall in ESR, clinical and radiological parameters showed improvement beyond 2 years of initiation of treatment in cases that had stopped treatment at 6 months. But the improvement was slow after six months even in cases who received 24 months of chemotherapy. There were no relapses in all the three groups. Conclusion. This study reinforces that chemotherapy tailored to the response of treatment (6-9months) is the rational therapy. This study gives an insight over the evolution of different regimes as well as gives an understanding of the clinical treatment. Level of Evidence. Level 1. No relevant financial disclosures or conflicts of interest from any of the authors

Osteosarcoma (OS) is an aggressive bone malignancy with a high relapse rate despite combined treatment with surgery and multiagent chemotherapy. As for other cancers, OS-associated microenvironment may contribute to tumor initiation, growth, and metastasis. We consider mesenchymal stromal cells (MSC) as a relevant cellular component of OS microenvironment, and have previously found that the interaction between MSC and tumor cells is bidirectional: tumor cells can modulate their peripheral environment that in turn becomes more favourable to tumor growth through metabolic reprogramming (1). Stem-like cells were derived from HOS osteosarcoma cell line by using the spherogenic system (2). CSC isolated from HOS (HOS-CSC) were co-coltured with MSC isolated from bone marrow. Cell lysates and supernatants were collected for the analysis of RNA expression and of secreted cytokines, by Q-RT-PCR and specific ELISA assays, respectively. Here, we determined the effects of MSC on OS stemness and migration, two major features associated with recurrence and chemoresistance. Recruitment of MSC to the tumor environment leads to enhanced proliferation of OS stem cells, which increase the expression levels of TGFβ1. The latter, in turn, could be responsible for the activation of NF-kB genes and IL-6 secretion by MSC. Pro-tumorigenic effects of MSC, via IL-6, including induction of HOS-CSC migration and sphere growth, can be counteracted by IL-6 neutralizing antibody. The presence of MSC is also responsible for increased expression of adhesion molecules involved in intra- or extra-vasation. Stromal cells in combination with OS spheres exploit a vicious cycle where the presence of CSC stimulates mesenchymal cytokine secretion, which in turn increases stemness, proliferation, migration, and metastatic potential of CSC. Furthermore, for the first time we identified a novel OS stem cell marker, the Met proto-oncogene, that is frequently overexpressed and is pathogenetically relevant in OS (2 and 3). Altogether, our data corroborates the concept that a comprehensive knowledge of the interplay between tumor and stroma that also includes the stem-like fraction of tumor cells is needed to develop novel and effective anti-cancer therapies

Summary. There is little consensus regarding the regime for treatment of tuberculosis of spine, although WHO has laid down guidelines couple of years back classifying spinal tuberculosis in Category 1. This study proves the efficacy of WHO regime in spinal tuberculosis by clinico-radiological evaluation. Introduction. The medical fraternity is divided over the duration of chemotherapy in cases spinal tuberculosis. WHO clearly recommend spinal tuberculosis under Category I, but not accepted by most clinicians. Patient and Methods. In this prospective study during the period between August 2005 and July 2012, a total of 76 cases were diagnosed and evaluated clinico-radiologically to test the efficacy of WHO protocol (2HRZE+4HR) in our hospital with a mean follow up of 50 months (30 – 80 months). Results. Spinal tuberculosis was seen in 56% of all osteoarticular tuberculosis. Maximum population was between 11–50 years, females were involved more than males (66%), and regional distribution was different in males (Lumbar) and females (Thoracic). Skip and multifocal lesions were seen in 13% (6 cases), more common in immune compromised cases. Pain was the most common symptom (95%) followed by constitutional symptoms. Radiographic changes were nonspecific, appear late and suggestive of tuberculosis in 53%case, MRI is very useful in diagnosing in 95% cases especially when X ray is contributory. ESR is useful tool for follow up of patients, elevated in 94%cases. Results were evaluated on clinical, hematological and radiological basis. Of the total 64cases (after dropouts, lost in follow up, mortality), 50 patients (78%) received treatment for 6 months and14 cases for more than 6months (P value<0.001). No MDR cases were present. In 50 patients fall in ESR at the end of 2 months was found to be statistically significant (P value<0.05) and hence were given a treatment for 6 months, the fall at the end of 6 months was highly significant (P value<0.001). In rest of the 14 cases the duration of treatment was given for more than 6 months as the trend of fall of ESR was not significant. MRI changes were assessed in the form of osteitis, osteitis with discitis, abscess formation and granulation tissue on initiation of treatment, completion of treatment and 6 months after completion of treatment. Conclusion and Discussion. The experience shows that spinal tuberculosis is common in a tertiary health care centre in India with diagnosis possible by combination of clinical evaluation and radiological evaluation. Statistical significance was found in clinical symptoms, ESR trends and MRI evaluation in cases receiving 6 months of chemotherapy. With this study, WHO short course chemotherapy was found to be effective in spinal tuberculosis, with no relapse over a period of 6 years

Summary Statement. Combination of sorafenib with irradiation achieved synergistic effect with dose reduction in both 143B and HOS cell lines. This demonstrated the potential application of sorafenib in the treatment of osteosarcoma metastasis and radiation resistance. Introduction. More than 20% of patients with osteosarcoma die of the disease within 5 years due to tumour relapse and metastasis. Identifying new treatment that works singly or in combination with conventional therapies is urgently required. We previously found that the Ras/Raf/MAPK pathway was associated with lung metastasis in a 143B inoculated osteosarcoma orthotopic mouse model. 1. Sorafenib, a multi-kinase inhibitor, has shown potent anticancer effect including in osteosarcoma. 2. through the inhibition of Raf-1 and other targets. 3. The aims of this study were to investigate effect of sorafenib on osteosarcoma cell lines with or without activated Ras/Raf/MAPK signalling and to decide whether sorafenib could enhance irradiation on these cells. Materials and Methods. Osteosarcoma cell lines 143B (HOS with Ras gene transfection), HOS and U2OS were used. Clonogenic assay was applied for assessing tumour growth and colony formation with or without treatment. Sorefenib was provided by Bayer gratis. Irradiation was performed using the Therapax DXT300 Orthovoltage Radiation System (Pantak, Connecticut, USA). Three doses of sorafenib (1, 2, 4 ug/ml) and three doses of radiation (50, 100, 200 cGy) were used with vehicle controls. In the combination therapy sorafenib was given at pre-, concurrent and post-irradiation. Each treatment was duplicated with the experiment being repeated once. Results. Sorafenib monotherapy achieved 50% inhibition (EC50) effects in all three tested cell lines with 7.05 ug/ml for 143B, 1.59 for HOS and 2.41 for U2OS. The 143B cell line was seriously resistant to irradiation with EC50 of 167 Gy, whilst other cell lines were relatively sensitive (HOS, 1.5 Gy and U2OS, 1.0 Gy). Combination of sorafenib with irradiation achieved synergistic effect with dose reduction in both 143B and HOS cell lines, but no obvious effect in U2OS cells. Discussion. Sorafenib demonstrated inhibitory effects on cell growth and colony formation even in a Ras/Raf/MAPK signalling activated osteosarcoma cell line, suggesting its potential application in the treatment of some metastatic osteosarcoma. Activated Ras/Raf/MAPK signalling is one of the mechanisms of radiation resistance and the synergistic effect of soratenib with irradiation combination therapy in this cell population indicated it's potential application in the treatment of irradiation resistant osteosarcoma. The dose reduction achieved by this combination could benefit patients with less specific side effects

Summary. In an in vitro tendon cell model, the tendon-specific gene expression up-regulation induced by PEMF negatively correlates with field intensity; moreover repeated lower-intensity PEMF treatments (1.5 mT) provokes a higher release of anti-inflammatory cytokines respect to the single treatment. Introduction. Tendon disorders represent a diagnostic and therapeutic challenge for physicians. Traditional treatments are characterised by a long recovery time and a high occurrence of injury relapses. Despite the growing clinical interest in pulsed electromagnetic fields (PEMFs) few studies on their effect on tendons and ligaments have been conducted. Tendon resident cells (TCs) are a mixed population, made up mostly by tenocytes and tendon stem/progenitor cells, which are responsible of the tissue homeostasis. Since studies on the effect of PEMFs on this cell population are conflicting, we evaluated the possible relation between PEMFs dosage and TCs’ response. In particular, we compared the in vitro effect of low and high PEMFs on TCs (PEMF-1.5 mT; PEMF-3 mT); moreover we assessed the results of repeated treatments (R-PEMF-1.5mT). Methods. TCs were isolated from the waste portion of semitendinosus and gracilis tendons of 7 healthy donors undergoing ACL reconstruction; at P4 they were exposed to different PEMF treatments (intensity: 1.5mT or 3mT; duration: 8 or 12 hours; periodicity: single or 3 treatments with an interval of 48h). Viability and DNA content were assessed by MTT and CyQuant, respectively, immediately at the end of the treatment (0d) and two days after (2d). Moreover, in order to accurately detected live and dead cells after the different treatments, Live&Dead staining was also assessed. At the same time points the expression of SCX, COL1A1 and VEGF were evaluated with RT-Real Time PCR, as well as the release of the cytokines TGFβ, IL6, IL10, IL1β, and TNFα by ELISA. Results. All the treatments applied for 12h increased TCs viability respect to untreated cells. However, respect to single PEMF-1.5mT, R-PEMF-1.5mT slightly decreased the TCs viability 2 days after 8 (−15%) and 12 hours (−9%) of exposure, whereas PEMF-3mT showed similar viability values. Nevertheless, the number of dead cells detected with Live&Dead assay was very low in all samples. All the tested PEMF treatments were able to relevantly enhance cell proliferation, with the exception of 12h R-PEMF-1.5mT, that reduces DNA content 2 day after treatment (−33%). All the treatments induced a significant increase of IL6, IL10 and TGFβ release respect to untreated cells (p<0.05), especially R-PEMF-1.5mT that showed higher values in comparison to the single PEMF-1.5mT treatment (p<.001). On the other hand pro-inflammatory cytokines (IL-1β and TNFα) production were not relevantly affected by any treatment. PEMF-3mT reduced the expression of tendon specific markers (SCX, COL1A1), whereas PEMF-1.5mT, above all as a single exposure, induced their up-regulation as well as the VEGF one, in comparison to untreated cells. Discussion/Conclusion. All PEMF treatments did not induced any cytotoxic events. Overall, a low intensity treatment, both single or repeated, allows to obtain a better in vitro TCs response in terms of anti-inflammatory cytokines release and tissue specific gene expression in comparison to higher electromagnetic field intensity (3 mT). In conclusion, these results suggest that PEMFs intensity negatively correlate with TCs in vitro response, whereas a repetition of low intensity treatment could positively influence tendon recovery. Further analyses on different models are needed to confirm these observations

Objectives

To elucidate the effects of age on the expression levels of the receptor activator of the nuclear factor-κB ligand (RANKL) and osteoclasts in the periodontal ligament during orthodontic mechanical loading and post-orthodontic retention.

We evaluated the possible induction of a systemic immune response to increase anti-tumour activity by the re-implantation of destructive tumour tissue treated by liquid nitrogen in a murine osteosarcoma (LM8) model. The tumours were randomised to treatment by excision alone or by cryotreatment after excision. Tissue from the tumour was frozen in liquid nitrogen, thawed in distilled water and then re-implanted in the same animal. In addition, some mice received an immunological response modifier of OK-432 after treatment. We measured the levels of interferon-gamma and interleukin-12 cytokines and the cytotoxicity activity of splenocytes against murine LM8 osteosarcoma cells. The number of lung and the size of abdominal metastases were also measured.

Re-implantation of tumour tissue after cryotreatment activated immune responses and inhibited metastatic tumour growth. OK-432 synergistically enhanced the anti-tumour effect. Our results suggest that the treatment of malignant bone tumours by reconstruction using autografts containing tumours which have been treated by liquid nitrogen may be of clinical value.

We studied 51 patients with osteo-articular tuberculosis who were divided into two groups. Group I comprised 31 newly-diagnosed patients who were given first-line antituberculous treatment consisting of isoniazid, rifampicin, ethambutol and pyrazinamide. Group II (non-responders) consisted of 20 patients with a history of clinical non-responsiveness to supervised uninterrupted antituberculous treatment for a minimum of three months or a recurrence of a previous lesion which on clinical observation had healed. No patient in either group was HIV-positive. Group II were treated with an immunomodulation regime of intradermal BCG, oral levamisole and intramuscular diphtheria and tetanus vaccines as an adjunct for eight weeks in addition to antituberculous treatment. We gave antituberculous treatment for a total of 12 to 18 months in both groups and they were followed up for a mean of 30.2 months (24 to 49). A series of 20 healthy blood donors served as a control group.

Twenty-nine (93.6%) of the 31 patients in group I and 14 of the 20 (70%) in group II had a clinicoradiological healing response to treatment by five months.

The CD4 cell count in both groups was depressed at the time of enrolment, with a greater degree of depression in the group-II patients (686 cells/mm³ (sd 261) and 545 cells/mm³ (sd 137), respectively; p < 0.05). After treatment for three months both groups showed significant elevation of the CD4 cell count, reaching a level comparable with the control group. However, the mean CD4 cell count of group II (945 cells/mm³ (sd 343)) still remained lower than that of group I (1071 cells/mm³ (sd 290)), but the difference was not significant. Our study has shown encouraging results after immunomodulation and antituberculous treatment in non-responsive patients. The pattern of change in the CD4 cell count in response to treatment may be a reliable clinical indicator.