Prognostic and Survival Factors in Myxofibrosarcomas

Aim. Our study aimed to determine prognostic factors for survival and recurrence in myxofibrosarcomas based on the experience of a single institution. Methods. Patients who had been diagnosed with a myxofibrosarcoma were identified from our database. Survival and recurrence were evaluated with Kaplan Meier survival curves for univariate and cox regression for multivariate analysis. Results. 174 patients with a diagnosis of myxofibrosarcoma were identified. Two patients were excluded due to incomplete information, leaving 172 patients with a mean age of 67 years. Surgery was undertaken in all but 6 patients. Five-year survival was better for myxofibrosarcomas when compared to other soft tissue sarcomas (63% versus 57%). Size, grade of tumour, age, and metastases were all found to be prognostic factors. Local recurrence occurred in 29 patients (17%) with an overall risk of 15% at 5 years. Previous inadvertent excision significantly raised this risk to 45%. Wide surgical margins and depth of tumour, however, had no impact on recurrence. Conclusion. Factors previously identified as prognostic did not demonstrate such a relationship in our study, highlighting the unpredictable nature of myxofibrosarcomas. Future treatment may lie in developing an understanding molecular basis of the tumour and directing therapies accordingly

Sacral chordoma: do the width of surgical margin and the use of photon/proton radiotherapy affect local disease control?

Purpose Chordoma is a rare but highly aggressive primary bone sarcoma that arises commonly from the sacrum. While en bloc resection has been the mainstay of the treatment, the role of resection margin in millimetres with/without adjuvant radiotherapy (RT) has been unknown. We investigated the prognostic impact of surgical margin width, adjuvant RT, and their combined factor for sacral chordoma. Methods Forty-eight patients who underwent surgical treatment between 1996 and 2016 were studied. Of these, 11 patients (23%) received adjuvant RT; photon RT in 7 (15%) and proton RT in 4 (8%). Margins were microscopically measured in millimetres from the resection surface to the closest tumour on histologic slides. Results The five year and ten year disease-specific survival was 88% and 58%, respectively, and the local recurrence (LR) rate was 48%. The LR rate with 0-mm, Conclusion This study identified the lowest risk of local failure in tumour resection with ≥ 1.5-mm margin or negative but < 1.5-mm margin with the use of adjuvant photon/proton radiotherapy for sacral chordoma. Early results of adjuvant proton RT demonstrated excellent local control

What is an adequate margin for infiltrative soft-tissue sarcomas?

Objectives What constitutes an adequate margin of resection for infiltrative subtypes of soft-tissue sarcomas remains unclear. We aimed to determine the prognostic significance of the margin in millimetres for myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). Methods 305 patients diagnosed with either a high-grade, localised MFS (n = 98) or UPS (n = 207) were included. The relationship of closest margin in millimetres to viable tumour and oncological outcomes was analysed. Results The overall local recurrence (LR) rate for all patients were 12%: 19% with positive margin and 10% with negative margin (p = 0.051). The LR rate was similar in patients with negative but Conclusion The resection margin, when measured as a metric distance, correlates with a reduction in LR, and appears to be more significant on local control than radiotherapy. To minimise the risk of LR, a margin distance of at least 10 mm is advocated for MFS and UPS

Low-grade soft-tissue sarcomas: What is an adequate margin for local disease control?

Background Whilst the resection margin is an established factor predictive of local control of soft-tissue sarcomas (STSs), the adequacy of margin width for low-grade STSs has been rarely described. We aimed to investigate the margin adequacy and its prognostic relevance in low-grade STSs. Methods 109 patients who underwent surgical treatment for a low-grade STS were studied. The prognostic value of margin status was evaluated according to the R–, R+1–classification, and width in millimetres. Results The 10-year local recurrence (LR) rates were 6%, 27%, 54% in R0, R1, and R2, respectively (p Conclusion Whilst negative margin provided local control over 90%, excellent local control was achieved with microscopic margins ≥2 mm. The role of margins is more important than radiotherapy in local control. Margins do not determine survival, but LR is associated with a poor prognosis

The adequacy of resection margin for non-infiltrative soft-tissue sarcomas

Objectives There remains no consensus on what constitutes an adequate margin of resection for non-infiltrative soft-tissue sarcomas (STSs). We aimed to investigate the role of resection margins in millimetres for non-infiltrative STSs. Methods 502 patients who underwent surgical resection for a localized, non-infiltrative, high-grade STSs were studied. The prognostic significance of margin width was analysed and compared with the conventional R- and R+1-classification of surgical margins. Results The overall local recurrence (LR) rate was 13%; 9% and 27% with negative and positive margins, respectively (p 5.0 mm. When classified by the R- (or R+1)-classification, the 5-year cumulative LR incidence was 8%, 23% (16%), and 31% for R0, R1, and R2, respectively, which did not stratify the LR risk with negative margins. On the other hand, an accurate risk stratification was possible by metric distance; the 5-year cumulative incidence of LR was 29%, 10%, and 1% with 0 mm, 0.1–5.0 mm, and >5.0 mm, respectively (p Conclusion While a negative margin is essential to optimize local control in patients with non-infiltrative STSs, surgical margin width greater than 5 mm minimises the risk of local failure regardless of the use of adjuvant radiotherapy

Hemodynamics during the 10-minute NASA Lean Test: evidence of circulatory decompensation in a subset of ME/CFS patients.

BACKGROUND: Lightheadedness, fatigue, weakness, heart palpitations, cognitive dysfunction, muscle pain, and exercise intolerance are some of the symptoms of orthostatic intolerance (OI). There is substantial comorbidity of OI in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The 10-minute NASA Lean Test (NLT) is a simple, point-of-care method that can aid ME/CFS diagnosis and guide management and treatment of OI. The objective of this study was to understand the hemodynamic changes that occur in ME/CFS patients during the 10-minute NLT. METHODS: A total of 150 ME/CFS patients and 75 age, gender and race matched healthy controls (HCs) were enrolled. We recruited 75 ME/CFS patients who had been sick for less than 4 years (\u3c 4 ME/CFS) and 75 ME/CFS patients sick for more than 10 years (\u3e 10 ME/CFS). The 10-minute NLT involves measurement of blood pressure and heart rate while resting supine and every minute for 10 min while standing with shoulder-blades on the wall for a relaxed stance. Spontaneously reported symptoms are recorded during the test. ANOVA and regression analysis were used to test for differences and relationships in hemodynamics, symptoms and upright activity between groups. RESULTS: At least 5 min of the 10-minute NLT were required to detect hemodynamic changes. The \u3c 4 ME/CFS group had significantly higher heart rate and abnormally narrowed pulse pressure compared to \u3e 10 ME/CFS and HCs. The \u3c 4 ME/CFS group experienced significantly more OI symptoms compared to \u3e 10 ME/CFS and HCs. The circulatory decompensation observed in the \u3c 4 ME/CFS group was not related to age or medication use. CONCLUSIONS: Circulatory decompensation characterized by increased heart rate and abnormally narrow pulse pressure was identified in a subgroup of ME/CFS patients who have been sick for \u3c 4 years. This suggests inadequate ventricular filling from low venous pressure. The 10-minute NLT can be used to diagnose and treat the circulatory decompensation in this newly recognized subgroup of ME/CFS patients. The \u3e 10 ME/CFS group had less pronounced hemodynamic changes during the NLT possibly from adaptation and compensation that occurs over time. The 10-minute NLT is a simple and clinically useful point-of-care method that can be used for early diagnosis of ME/CFS and help guide OI treatment

Suspended manufacture of biological structures

We present a novel method of extrusion-based ALM for the production of cell-laden strucutres from low viscosity polymers. The traditional planar print bed is replaced with a bed of micoparticulate fluid gel. During the extrusion process, the fluid gel is displaced whilst providing a support strucutre for the low viscosity material allowing manufacture of relatively complex geometries. The extruded structure can then be easily removed from this self-healing fluid bed. For this study, a bi-layered cell-seeded construct was produced to model the osteochondral junction. Osteochondral plugs were produced by the addition of chondrocytes and osteoblasts to 1.5%w/v gellan and 1.5%w/v gellan-5% nano-hydroxyapatite respectively. The consecutive extrusion of these two solutions into the fluid bed followed by further ionic crosslinking produced the bi-layered construct that was implant into a femoral condyle defect in vitro. Cell viability following extrusion was confirmed using calcein AM/PI live/dead staining showing excellent viability. Constructs were then sectioned, and qRT-PCR was performed, showing a native collagen phenotype across the construct with evidence of matrix markers in the cartilage-like region which were also identified using fluroescent-IHC. Constructs were also tested for their bulk relaxation properties. Addition of nano-hydroxyapatite in the bone-like region resulted in a faster, more elastic relaxation than gellan alone, something that has previously been reported to favour osteogenic differentiation. Please click Additional Files below to see the full abstract

Maternally expressed, paternally imprinted, embryonic non-coding RNA are expressed in osteosarcoma, Ewing sarcoma and spindle cell sarcoma

In a human embryo it takes 8 weeks after fertilisation for the skeleton to begin to form, one of the last organs to develop before becoming a foetus. Mesenchymal progenitors, derived from neural crest cells, differentiate into chondrocytes where the skeleton is generated as a mostly cartilage template. Other mesenchymal progenitors envelop the template, activate runt related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP2) and differentiate into osteoblasts, where an osteoid matrix is secreted and subsequently mineralised to become bone.1 During development and up to late adolescence, cellular proliferation enabling skeletal growth is restricted to the metaphysis and epiphyseal line or “growth plate”. It is in the growth plate of long bones where most bone cancers develop, hence the predominantly childhood incidence of the cancer. Primitive mesenchymal cells undergo transformation to form a heterogeneous group of bone malignancies. The most common type of bone cancer in children is osteosarcoma, mostly initiated by tumour protein p53 (TP53) mutations. The second most common type of bone cancer in children is Ewing sarcoma, mostly initiated by a EWS RNA binding protein 1-Fli-1 proto-oncogene, ETS transcription factor (EWSR1-FLI1) fusion. There are an average of 160 and 55 new cases of osteosarcoma and Ewing sarcoma, respectively, every year in the UK. Five-year survival for both cancer types is 50% when diagnosed early. Five-year survival is 15% when lung metastases are present at diagnosis. Treatment progress for bone cancer is poor when compared to other cancers such as breast where there is a twenty-year survival of 70%. Bone cancer requires extensive and sometimes disabling multimodal treatment. Chemotherapy for osteosarcoma includes methotrexate, cisplatin and doxorubicin, which were developed in the 1940’s and 1970’s. Chemotherapy for Ewing sarcoma includes vincristine, ifosfamide and etoposide, which were developed in the 1960’s and 1980’s. If the tumour responds well to chemotherapy and radiotherapy, wide area resection or amputation is performed. New understanding of bone cancer biology leading to better diagnosis and better treatments is required