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We present a novel case of a malignant transformation of an extremity soft tissue angioleiomyoma to leiomyosarcoma in a man in his late 70s who presented with a painful and increasing lump on his anterior tibia. Initial imaging and biopsy showed a benign angioleiomyoma which was excised for symptomatic reasons. An analysis of the resulting specimen revealed a 50×42×15 mm smooth muscle neoplasm consistent with angioleiomyoma with a 22×11 mm entirely intralesional nodular component in keeping with a grade 1 leiomyosarcoma. The malignant constituent of the lesion was entirely encased in benign angioleiomyoma negating the need for further surgery. Systemic staging investigation revealed no evidence of metastatic disease spread final staging as per the eighth edition of the American Joint Committee on Cancer (AJCC) Staging T1N0M0 R0 Stage 1 a.
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Angiomioma , Leiomiossarcoma , Tíbia , Humanos , Masculino , Leiomiossarcoma/patologia , Leiomiossarcoma/cirurgia , Leiomiossarcoma/diagnóstico por imagem , Tíbia/patologia , Tíbia/diagnóstico por imagem , Angiomioma/patologia , Angiomioma/cirurgia , Angiomioma/diagnóstico por imagem , Idoso , Transformação Celular Neoplásica/patologia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Biópsia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/diagnóstico por imagemRESUMO
Aims: Most patients with advanced malignancy suffer bone metastases, which pose a significant challenge to orthopaedic services and burden to the health economy. This study aimed to assess adherence to the British Orthopaedic Oncology Society (BOOS)/British Orthopaedic Association (BOA) guidelines on patients with metastatic bone disease (MBD) in the UK. Methods: A prospective, multicentre, national collaborative audit was designed and delivered by a trainee-led collaborative group. Data were collected over three months (1 April 2021 to 30 June 2021) for all patients presenting with MBD. A data collection tool allowed investigators at each hospital to compare practice against guidelines. Data were collated and analyzed centrally to quantify compliance from 84 hospitals in the UK for a total of 1,137 patients who were eligible for inclusion. Results: A total of 846 patients with pelvic and appendicular MBD were analyzed, after excluding those with only spinal metastatic disease. A designated MBD lead was not present in 39% of centres (33/84). Adequate radiographs were not performed in 19% of patients (160/846), and 29% (247/846) did not have an up-to-date CT of thorax, abdomen, and pelvis to stage their disease. Compliance was low obtaining an oncological opinion (69%; 584/846) and prognosis estimations (38%; 223/846). Surgery was performed in 38% of patients (319/846), with the rates of up-to-date radiological investigations and oncology input with prognosis below the expected standard. Of the 25% (215/846) presenting with a solitary metastasis, a tertiary opinion from a MBD centre and biopsy was sought in 60% (130/215). Conclusion: Current practice in the UK does not comply with national guidelines, especially regarding investigations prior to surgery and for patients with solitary metastases. This study highlights the need for investment and improvement in care. The recent publication of British Orthopaedic Association Standards for Trauma (BOAST) defines auditable standards to drive these improvements for this vulnerable patient group.
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Neoplasias Ósseas , Ortopedia , Humanos , Estudos Prospectivos , Radiografia , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/secundário , TóraxRESUMO
BACKGROUND: Megaprosthetic replacement (MPR) of the femur is typically reserved for salvage or oncological reconstruction. Presently little is known about the provision of femoral MPRs performed nationally, the trends in indications for their use, and their outcomes beyond published unit-level data. Although the National Joint Registry (NJR) collects data as part of a mandatory arthroplasty audit process, MPR data entry on this platform is thought to be inconsistent. The aim of this study is to determine current trends for femoral MPR procedures as submitted to the NJR. METHODS: Data for all procedures submitted to the NJR using the following implants were extracted: METS (Stanmore/Stryker), MUTARS (Implantcast), Segmental (Zimmer), GMRS (Stryker) and MEGA C (LINK). Pseudoanonymized data were analyzed through the NJR's research Data Access Portal and are reported using descriptive statistics. RESULTS: A total of 1781 procedures were identified. Submitted cases increased for primary and revision hip and knee categories over the study period, although they plateaued in recent years. MPR implants were most commonly used in revision hip arthroplasty procedures. MPR use for the management of peri-prosthetic fractures has increased and now represents the most commonly reported indication for MPR use in both hip and knee revision categories. Few centers submitted large MPR case volumes (which were noted to be lower than published unit case series, indicating NJR under-reporting), and the vast majority of centers submitting MPR cases did so in low volume. CONCLUSIONS: Due to the limitations identified, reported case volumes must be interpreted with caution. An MPR-specific NJR data entry form has been developed to allow more accurate and tailored reporting of MPR procedures, to support specialist service provision, and to provide meaningful data for future research.
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BACKGROUND: Leiomyosarcomas are aggressive malignancies which can occur on the trunk and extremities whose pathogenesis is poorly understood. We aim to quantify the prognostic impact of various clinical and pathological markers on survival and recurrence of leiomyosarcomas. METHODS: We conducted a systematic review as per PRISMA protocol. Survival, local recurrence, and metastasis were the outcome measures. Data were extracted from the studies for the outcome variables; the resultant odds ratios (OR) and 95% confidence interval (CI) were used for the synthesis of a forest plot. RESULTS: Our search revealed thirteen studies comprising 1380 patients. Seven of these 13 publications were since 2012. Our analysis showed that tumor size larger than 5 cm adversely affected the outcome with an OR 3.39 (2.26-5.10, p < 0.01). Other factors which reduced the overall survival were positive margins of excision OR 2.12 (1.36-3.32, p < 0.01). A reduced risk of metastasis has strongly associated the use of radiotherapy with OR 10.84 (4.41-26.61, p < 0.01). Only a few studies analyzed the impact of factors on local recurrence. CONCLUSIONS: Size larger than 5 cm and positive margins of excision are associated with poor overall survival. In comparison, the use of adjuvant radiotherapy was associated with a lower metastatic rate. There is a need for methodically high-quality studies with more uniform study design and reporting to evaluate the impact of various risk factors on local recurrence and metastases. LEVEL OF EVIDENCE: Level 1 Prognostic.
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Leiomiossarcoma , Neoplasias de Tecidos Moles , Extremidades/patologia , Extremidades/cirurgia , Humanos , Leiomiossarcoma/patologia , Leiomiossarcoma/terapia , Margens de Excisão , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias de Tecidos Moles/cirurgiaRESUMO
There is a paucity of literature analysing the importance of leadership within trauma and orthopaedics. However, such skills are essential to make an orthopaedic surgeon proficient in their various roles. This literature review on leadership within orthopaedics enables an understanding of current issues. A narrative literature review was conducted using Pubmed, Medline and The National Centre for Biotechnology databases. The search string used to conduct the narrative literature review was (orthopaedic) and (leadership[Title]). The articles were screened by title, abstract and full text. A reference search was subsequently conducted on these papers using the same inclusion and exclusion criteria. The papers then underwent a thematic analysis to understand the issues surrounding leadership in orthopaedics. The critical themes recognised were quality improvement, training, women in leadership, inequality and traits of a leader. Through reviewing the themes in this article, a framework was developed to identify the current issues and potential avenues of advancing orthopaedic leadership. This narrative literature review has demonstrated a paucity of research in orthopaedic leadership. Further work would create a robust evidence base, outline ideal orthopaedic leadership and standardise training to create better orthopaedic leaders.
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Procedimentos Ortopédicos , Ortopedia , Atenção à Saúde , Feminino , Humanos , LiderançaRESUMO
INTRODUCTION: Soft tissue sarcomas (STS) are a group of rare malignant tumours that can occur at almost any anatomical location in patients of any age, which often present to health care professional working outside a recognised sarcoma service. A review of foot and ankle STSs was conducted, reporting on patient and tumour characteristics, and patient outcome following surgery performed within and outside our sarcoma service. PATIENTS AND METHODS: A retrospective review of all foot and ankle STSs managed by our sarcoma service over a 14 year period was performed. Patient demographics, tumour characteristics, management and patient outcomes including recurrence rates and survival were analysed. RESULTS: Twenty-six patients were analysed (16F:10M) with a mean age of 57.7 years (range 17-87). The mean follow-up was 6.3 years (range 1-16). Sixteen tumours involved the foot, nine the ankle, and one spanned the foot and ankle. Mean tumour size was 4.3 cm (range 0.8-15), although 61% of cases were smaller than 4 cm, and almost one third of cases smaller than 1 cm. Seven of 26 (27%) cases were diagnosed after an unplanned excision performed by non sarcoma surgeons. These patients were more likely to undergo an incomplete tumour excision (p < 0.001), suffer local recurrence (p = 0.001), and eventually undergo a secondary amputation (p = 0.034) than those patients managed exclusively by a sarcoma service. Overall, 12 (46%) patients died of their disease during follow up, equating to a five-year survival rate of 69%. CONCLUSION: Our data shows that unplanned excisions continue to be performed on foot and ankle STSs, and that these have detrimental effects on patients. Despite this, our results also show that these complex patients can be managed successfully when referred appropriately to a sarcoma service, prior to any surgical treatment. This highlights the importance of vigilance amongst all health care professionals managing any foot or ankle lumps, regardless of their size.
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Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tornozelo/cirurgia , Articulação do Tornozelo , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Sarcoma/cirurgia , Adulto JovemRESUMO
BACKGROUND: Skeletal muscle wasting and dysfunction are common characteristics noted in people who suffer from chronic kidney disease (CKD). The mechanisms by which this occurs are complex, and although progress has been made, the key underpinning mechanisms are not yet fully elucidated. With work to date primarily conducted in nephrectomy-based animal models, translational capacity to our patient population has been challenging. This could be overcome if rationale developing work could be conducted in human based models with greater translational capacity. This could be achieved using cells derived from patient biopsies, if they retain phenotypic traits noted in vivo. METHODS: Here, we performed a systematic characterization of CKD derived muscle cells (CKD; n = 10; age: 54.40 ± 15.53 years; eGFR: 22.25 ± 13.22 ml/min/1.73 m2 ) in comparison with matched controls (CON; n = 10; age: 58.66 ± 14.74 years; eGFR: 85.81 ± 8.09 ml/min/1.73 m2 ). Harvested human derived muscle cells (HDMCs) were taken through proliferative and differentiation phases and investigated in the context of myogenic progression, inflammation, protein synthesis, and protein breakdown. Follow up investigations exposed HDMC myotubes from each donor type to 0, 0.4, and 100 nM of IGF-1 in order to investigate any differences in anabolic resistance. RESULTS: Harvested human derived muscle cells isolated from CKD patients displayed higher rates of protein degradation (P = 0.044) alongside elevated expression of both TRIM63 (2.28-fold higher, P = 0.054) and fbox32 (6.4-fold higher, P < 0.001) in comparison with CONs. No differences were noted in rates of protein synthesis under basal conditions (P > 0.05); however, CKD derived cells displayed a significant degree of anabolic resistance in response to IGF-1 stimulation (both doses) in comparison with matched CONs (0.4 nm: P < 0.001; 100 nM: P < 0.001). CONCLUSIONS: In summary, we report for the first time that HDMCs isolated from people suffering from CKD display key hallmarks of the well documented in vivo phenotype. Not only do these findings provide further mechanistic insight into CKD specific cachexia, but they also demonstrate this is a reliable and suitable model in which to perform targeted experiments to begin to develop novel therapeutic strategies targeting the CKD associated decline in skeletal muscle mass and function.
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Caquexia , Insuficiência Renal Crônica , Animais , Caquexia/metabolismo , Humanos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Insuficiência Renal Crônica/metabolismoRESUMO
BACKGROUND: People with chronic kidney disease (CKD) experience skeletal muscle wasting, reduced levels of physical function and performance, and chronic systemic inflammation. While it is known that a relationship exists between inflammation and muscle wasting, the association between inflammation and physical function or performance in CKD has not been well studied. Exercise has anti-inflammatory effects, but little is known regarding the effect of moderate intensity exercise. This study aimed to (i) compare systemic and intramuscular inflammation between CKD stage G3b-5 and non-CKD controls; (ii) establish whether a relationship exists between physical performance, exercise capacity and inflammation in CKD; (iii) determine changes in systemic and intramuscular inflammation following 12 weeks of exercise; and (iv) investigate whether improving inflammatory status via training contributes to improvements in physical performance and muscle mass. METHODS: This is a secondary analysis of previously collected data. CKD patients stages G3b-5 (n = 84, n = 43 males) and non-CKD controls (n = 26, n = 17 males) underwent tests of physical performance, exercise capacity, muscle strength and muscle size. In addition, a subgroup of CKD participants underwent 12 weeks of exercise training, randomized to aerobic (AE, n = 21) or combined (CE, n = 20) training. Plasma and intramuscular inflammation and myostatin were measured at rest and following exercise. RESULTS: Tumour necrosis factor-α was negatively associated with lower $^{^{^{.}}}{\rm V}$O2Peak (P = 0.01), Rectus femoris-cross sectional area (P = 0.002) and incremental shuttle walk test performance (P < 0.001). Interleukin-6 was negatively associated with sit-to-stand 60 performances (P = 0.006) and hand grip strength (P = 0.001). Unaccustomed exercise created an intramuscular inflammatory response that was attenuated following 12 weeks of training. Exercise training did not reduce systemic inflammation, but AE training did significantly reduce mature myostatin levels (P = 0.02). Changes in inflammation were not associated with changes in physical performance. CONCLUSIONS: Systemic inflammation may contribute to reduced physical function in CKD. Twelve weeks of exercise training was unable to reduce the level of chronic systemic inflammation in these patients, but did reduce plasma myostatin concentrations. Further research is required to further investigate this.
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Falência Renal Crônica , Insuficiência Renal Crônica , Exercício Físico , Terapia por Exercício , Feminino , Força da Mão , Humanos , Inflamação/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Atrofia Muscular/complicações , Miostatina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapiaRESUMO
Coronavirus disease-2019 (COVID-19) is the infectious disease caused by the recently discovered coronavirus, SARS-CoV2. This new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. The number of publications with regard to COVID-19-related information is exponentially increasing, but there are also some retracted papers appearing on PubMed, including those retracted from The Lancet Global Health and the New England Journal of Medicine. In a PubMed search for "COVID," there were 1595 articles by April 1, 2020. As of June 30, the number of articles has now reached 25,913. In this editorial, 4 specific areas of information are looked at but the principles apply to many other areas of medicine. The specifics looked at are PPE for tracheostomy, testing for COVID-19, pregnancy and COVID-19, and surgical expectations during redeployment. We must make no mistake that we are seeing a disease that modern medicine has never encountered before. This article is not aimed at belittling or dismissing any of the advice of the Royal Colleges' or PHE advice, but it demonstrates the tsunami of information and the ambiguity that surgeons are experiencing throughout the UK right now. This is unlikely to be the end of progression regarding healthcare planning and development for unencountered viruses9. In the next few months and beyond, there are likely to be adaptions and revisions of more documents advising on various aspects of healthcare with regard to COVID-19 management and for possible future viruses not yet seen by the modern world before.
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COVID-19 , Controle de Infecções , Procedimentos de Cirurgia Plástica , Centro Cirúrgico Hospitalar , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Controle de Infecções/instrumentação , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Disseminação de Informação , Inovação Organizacional , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/tendências , SARS-CoV-2 , Centro Cirúrgico Hospitalar/organização & administração , Centro Cirúrgico Hospitalar/tendênciasAssuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Sarcoma/cirurgia , Retalhos Cirúrgicos , Reino UnidoRESUMO
BACKGROUND: Delivering uninterrupted cancer treatment to patients with musculoskeletal tumors has been essential during the rapidly evolving coronavirus 2019 (COVID-19) pandemic, as delays in management can be detrimental. Currently, the risk of contracting COVID-19 in hospitals when admitted for surgery and the susceptibility due to adjuvant therapies and associated mortality due to COVID-19 is unknown, but knowledge of these potential risks would help treating clinicians provide appropriate cancer care. QUESTIONS/PURPOSES: (1) What is the risk of hospital-acquired COVID-19 in patients with musculoskeletal tumors admitted for surgery during the initial period of the pandemic? (2) What is the associated mortality in patients with musculoskeletal tumors who have contracted COVID-19? (3) Are patients with musculoskeletal tumors who have had neoadjuvant therapy (chemotherapy or radiation) preoperatively at an increased risk of contracting COVID-19? (4) Is a higher American Society of Anesthesiologists (ASA) grade in patients with musculoskeletal tumors associated with an increased risk of contracting COVID-19 when admitted to the hospital for surgery? METHODS: This retrospective, observational study analyzed patients with musculoskeletal tumors who underwent surgery in one of eight specialist centers in the United Kingdom, which included the five designated cancer centers in England, one specialist soft tissue sarcoma center, and two centers from Scotland between March 12, 2020 and May 20, 2020. A total of 347 patients were included, with a median (range) age of 53 years (10 to 94); 60% (207 of 347) were men, and the median ASA grade was II (I to IV). These patients had a median hospital stay of 8 days (0 to 53). Eighteen percent (61 of 347) of patients had received neoadjuvant therapy (8% [27] chemotherapy, 8% [28] radiation, 2% [6] chemotherapy and radiation) preoperatively. The decision to undergo surgery was made in adherence with United Kingdom National Health Service and national orthopaedic oncology guidelines, but specific data with regard to the number of patients within each category are not known. Fifty-nine percent (204 of 347) were negative in PCR testing done 48 hours before the surgical procedure; the remaining 41% (143 of 347) were treated before preoperative PCR testing was made mandatory, but these patients were asymptomatic. All patients were followed for 30 days postoperatively, and none were lost to follow-up during that period. The primary outcome of the study was contracting COVID-19 in the hospital after admission. The secondary outcome was associated mortality after contracting COVID-19 within 30 days of the surgical procedure. In addition, we assessed whether there is any association between ASA grade or neoadjuvant treatment and the chances of contracting COVID-19 in the hospital. Electronic patient record system and simple descriptive statistics were used to analyze both outcomes. RESULTS: Four percent (12 of 347) of patients contracted COVID-19 in the hospital, and 1% (4 of 347) of patients died because of COVID-19-related complications. Patients with musculoskeletal tumors who contracted COVID-19 had increased mortality compared with patients who were asymptomatic or tested negative (odds ratio 55.33 [95% CI 10.60 to 289.01]; p < 0.001).With the numbers we had, we could not show that adjuvant therapy had any association with contracting COVID-19 while in the hospital (OR 0.94 [95% CI 0.20 to 4.38]; p = 0.93). Increased ASA grade was associated with an increased likelihood of contracting COVID-19 (OR 58 [95% CI 5 to 626]; p < 0.001). CONCLUSION: Our results show that surgeons must be mindful and inform patients that those with musculoskeletal tumors are at risk of contracting COVID-19 while admitted to the hospital and some may succumb to it. Hospital administrators and governmental agencies should be aware that operations on patients with lower ASA grade appear to have lower risk and should consider restructuring service delivery to ensure that procedures are performed in designated COVID-19-restricted sites. These measures may reduce the likelihood of patients contracting the virus in the hospital, although we cannot confirm a benefit from this study. Future studies should seek to identify factors influencing these outcomes and also compare surgical complications in those patients with and without COVID-19. LEVEL OF EVIDENCE: Level III, therapeutic study.
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Neoplasias Ósseas/terapia , COVID-19/complicações , Infecção Hospitalar/complicações , Neoplasias de Tecidos Moles/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , COVID-19/mortalidade , Criança , Infecção Hospitalar/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Neoplasias de Tecidos Moles/mortalidade , Reino Unido/epidemiologia , Adulto JovemRESUMO
AIMS: Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients. METHODS: MEDLINE (PubMed), EMBASE (Ovid), Cochrane, and CINAHL databases were searched focusing on VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, or wound complication rates. RESULTS: In all, 17 studies published from 1998 to 2018 met the inclusion criteria for the systematic review. The mean incidence of all VTE events in orthopaedic oncology patients was 10.7% (1.1% to 27.7%). The rate of PE was 2.4% (0.1% to 10.6%) while the rate of lethal PE was 0.6% (0.0% to 4.3%). The overall rate of DVT was 8.8% (1.1% to 22.3%) and the rate of symptomatic DVT was 2.9% (0.0% to 6.2%). From the studies that screened all patients prior to hospital discharge, the rate of asymptomatic DVT was 10.9% (2.0% to 20.2%). The most common risk factors identified for VTE were endoprosthetic replacements, hip and pelvic resections, presence of metastases, surgical procedures taking longer than three hours, and patients having chemotherapy. Mean incidence of VTE with and without chemical prophylaxis was 7.9% (1.1% to 21.8%) and 8.7% (2.0% to 23.4%; p = 0.11), respectively. No difference in the incidence of bleeding or wound complications between prophylaxis groups was reported. CONCLUSION: Current evidence is limited to guide clinicians. It is our consensus opinion, based upon logic and deduction, that all patients be considered for both mechanical and chemical VTE prophylaxis, particularly in high-risk patients (pelvic or hip resections, prosthetic reconstruction, malignant diagnosis, presence of metastases, or surgical procedures longer than three hours). Additionally, the surgeon must determine, in each patient, if the risk of haemorrhage outweighs the risk of VTE. No individual pharmacological agent has been identified as being superior in the prevention of VTE events. Cite this article: Bone Joint J 2020;102-B(12)1743:-1751.
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Neoplasias Ósseas/cirurgia , Fármacos Hematológicos/uso terapêutico , Procedimentos Ortopédicos/efeitos adversos , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Neoplasias Ósseas/complicações , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Fármacos Hematológicos/efeitos adversos , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Incidência , Procedimentos Ortopédicos/métodos , Fatores de Risco , Meias de Compressão , Filtros de Veia Cava , Tromboembolia Venosa/etiologiaRESUMO
Soft tissue sarcomas (STS) are rare, malignant tumours with a generally poor prognosis. Our aim was to explore the potential of cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) analysis to track non-metastatic STS patients undergoing attempted curative treatment. The analysed cohort (n = 29) contained multiple STS subtypes including myxofibrosarcomas, undifferentiated pleomorphic sarcomas, leiomyosarcomas, and dedifferentiated liposarcomas amongst others. Perioperative cfDNA levels trended towards being elevated in patients (p = 0.07), although did not correlate with tumour size, grade, recurrence or subtype, suggesting a limited diagnostic or prognostic role. To characterise ctDNA, an amplicon panel covering three genes commonly mutated in STSs was first trialled on serial plasma collected from nine patients throughout follow-up. This approach only identified ctDNA in 2.5% (one in 40) of the analysed samples. Next custom-designed droplet digital PCR assays and Ion AmpliSeq™ panels were developed to track single nucleotide variants identified in patients' STSs by whole exome sequencing (1-6 per patient). These approaches identified ctDNA in 17% of patients. Although ctDNA was identified before radiologically detectable recurrence in two cases, the absence of demonstrable ctDNA in 83% of cases highlights the need for much work before circulating nucleic acids can become a useful means to track STS patients.
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Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Mutação , Sarcoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , DNA Tumoral Circulante/análise , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sarcoma/genética , Sarcoma/cirurgia , Taxa de SobrevidaRESUMO
This article provides a brief overview of the current COVID-19 pandemic crisis and the impact on trauma and orthopaedic surgeons. The principles of protect, avoid, restrict and abbreviate are recommended. Coordination of response, communication and support are also important. The versatility of orthopaedic surgeons lends them to having an important role.
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Neoplasias Ósseas , Sarcoma , Adulto , Humanos , Osteossarcoma , Dor , Neoplasias de Tecidos Moles , Adulto JovemRESUMO
Following treatment 40% of soft tissue sarcoma (STS) patients suffer disease recurrence. In certain cancers circulating cell free DNA (cfDNA) and circulating tumour-derived DNA (ctDNA) characteristics correlate closely with disease burden, making them exciting potential sources of biomarkers. Despite this, the circulating nucleic acid characteristics of only 2 STS patients have been reported to date. To address this we used an Ion AmpliSeq™ panel custom specifically designed for STS patients to conduct a genetic characterisation of plasma cfDNA, buffy coat (germline) DNA and where available Formalin-Fixed Paraffin-Embedded (FFPE) primary STS tissue DNA in a cohort of 11 metastatic STS patients. We found that total cfDNA levels were significantly elevated in the STS patients analysed, and weakly correlated with disease burden. Using our Ion AmpliSeq™ panel we also successfully detected ctDNA in 4/11 (36%) patients analysed with a wide variety of STS subtypes and disease burdens. This evidence included the presence of cancer associated TP53 / PIK3CA mutations in 2 patients' plasma and matched primary STS tumour tissue, and in the plasma alone for 2 patients. We also identified 2 potential examples of allelic loss of heterozygosity in an additional patient's STS DNA and cfDNA. This is the largest study performed characterising STS patient cfDNA/ctDNA and confirms that the field remains an attractive potential source of novel STS biomarkers. Further work is required to investigate the circulating nucleic acid characteristics of individual STS subtypes, and the potential prognostic or therapeutic roles that cfDNA/ctDNA may hold for patients with these complex tumours.
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Soft tissue sarcomas (STS) are a diverse group of heterogeneous malignant tumours derived from mesenchymal tissues. Over 50 different STS subtypes are recognised by WHO, which show a wide range of different biological behaviours and prognoses. At present, clinicians managing this complex group of tumours face several challenges. This is reflected by the relatively poor outcome of patients with STSs compared with many other solid malignant tumours. These include difficulties securing accurate diagnoses, a lack of effective systemic treatments and absence of any sensitive circulating biomarkers to monitor patients throughout their treatment and follow-up. In order to progress STS's cells must evade the usual cellular proliferative checkpoints, and then activate a telomere maintenance mechanism in order to achieve replicative immortality. The purpose of this review is to provide an overview of STS genetics focusing particularly on these mechanisms. We will also highlight some of the key barriers to improving outcome for patients with STS, and hypothesise how a better understanding of these genetic characteristics may impact on future STS management.