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Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. Materials and methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Results: A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Conclusion: Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.
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Neoplasias Óseas , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Anciano , Estudios Retrospectivos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Neoplasias Óseas/secundario , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Resultado del TratamientoRESUMEN
In this special edition update on soft tissue sarcomas (STS), we cover classifications, emerging technologies, prognostic tools, radiation schemas, and treatment disparities in extremity and truncal STS. We discuss the importance of enhancing local control and reducing complications, including the role of innovative imaging, surgical guidance, and hypofractionated radiation. We review advancements in systemic and immunotherapeutic treatments and introduce disparities seen in this vulnerable population that must be considered to improve overall patient care.
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Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Radioterapia Adyuvante , Extremidades , Pronóstico , Torso , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugíaRESUMEN
BACKGROUND AND OBJECTIVES: Given advances in therapies, endoprosthetic reconstruction (EPR) in metastatic bone disease (MBD) may be increasingly indicated. The objectives were to review the indications, and implant and patient survivorship in patients undergoing EPR for MBD. METHODS: A review of patients undergoing EPR for extremity MBD between 1992 and 2022 at two centers was performed. Surgical data, implant survival, patient survival, and implant failure modes were examined. RESULTS: One hundred fifteen patients were included with a median follow-up of 14.9 months (95% confidence interval [CI]: 9.2-19.3) and survival of 19.4 months (95% CI: 13.6-26.1). The most common diagnosis was renal cell carcinoma (34/115, 29.6%) and the most common location was proximal femur (43/115, 37.4%). Indications included: actualized fracture (58/115, 50.4%), impending fracture (30/115, 26.1%), and failed fixation (27/115, 23.5%). Implant failure was uncommon (10/115, 8.7%). Patients undergoing EPR for failed fixation were more likely to have renal or lung cancer (p = 0.006). CONCLUSIONS: EPRs were performed most frequently for renal cell carcinoma and in patients with a relatively favorable survival. EPR was indicated for failed previous fixation in 23.5% of cases, emphasizing the importance of predictive survival modeling. EPR can be a reliable and durable surgical option for patients with MBD.
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Neoplasias Óseas , Carcinoma de Células Renales , Neoplasias Femorales , Neoplasias Renales , Humanos , Diseño de Prótesis , Carcinoma de Células Renales/cirugía , Supervivencia , Falla de Prótesis , Resultado del Tratamiento , Factores de Riesgo , Neoplasias Femorales/cirugía , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Neoplasias Renales/cirugía , Extremidades/patología , Estudios Retrospectivos , ReoperaciónRESUMEN
BACKGROUND: Platelets play a role in venous thromboembolism (VTE) and in mediating colorectal cancer (CRC) progression. Still, platelets' role in hypercoagulability after surgical intervention for metastatic bone disease (MBD) is ill-defined. METHODS: In this quantitative observational study, we utilized a high-resolution imaging approach to temporally examine platelet procoagulant membrane dynamics (PMD) in four patients with MBD from primary CRC (CRC/MBD), before and after surgical intervention, over a 6-month period. We coupled this investigation with thrombelastography, quantitative plasma shotgun proteomics, and biochemical analysis. RESULTS: The plasma of CRC/MBD patients was enriched in ADAM1a, ADAMTS7, and physiological ligands for platelet glycoprotein-VI/spleen tyrosine kinase (GPVI/Syk) activation. Thromboprophylaxis attenuated procoagulation upon its initial prescription (post-operative day one, POD1); however, all patients experienced rebound procoagulation between POD3 and POD14, which was associated with Syk activation (Y525/Y526) in all patients, and a VTE event in two patients. Plasma levels of DNA-histone complexes increased steadily after surgery and remained elevated throughout the study period. Additionally, we increasingly sighted both homotypic and heterotypic platelet microaggregates after surgery in CRC/MBD patients, but not in healthy control participants' plasma. CONCLUSIONS: Our data elucidates the cell biology of a prothrombo-inflammatory state caused by disease and vascular injury, and recalcitrant to thromboprophylaxis. New mechanistic insights into hypercoagulability in CRC/MBD patients may identify novel drug targets for effective thromboprophylaxis type and duration after orthopaedic surgery.
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BACKGROUND: The aims of this study are to (1) determine whether fixation of metastatic long bone fractures with an intramedullary nail (IMN) influences the incidence of lung metastasis in comparison to arthroplasty or ORIF (Arthro/ORIF); and (2) assess this relationship in primary tumor types; and (3) to assess survival implications of lung metastasis after surgery. METHODS: Retrospective cohort study investigating 184 patients (107 IMN, and 77 Arthro/ORIF) surgically treated for metastatic long bone fractures. Patients were required to have a single surgically treated impending or established pathologic fracture of a long bone, pre-operative lung imaging (lung radiograph or computed tomography) and post-operative lung imaging within 6 months of surgery. Primary cancer types included were breast (n = 70), lung (n = 43), prostate (n = 34), renal cell (n = 37). Statistical analyses were conducted using two-tailed Fisher's exact tests, and Kaplan-Meier survival analyses. RESULTS: Patients treated with IMN and Arthro/ORIF developed new or progressive lung metastases following surgery at an incidence of 34 and 26%, respectively. Surgical method did not significantly influence lung metastasis (p = 0.33). Furthermore, an analysis of primary cancer subgroups did not yield any differences between IMN vs Arthro/ORIF. Median survival for the entire cohort was 11 months and 1-year overall survival was 42.7% (95% CI: 35.4-49.8). Regardless of fixation method, the presence of new or progressive lung metastatic disease at follow up imaging study was found to have a negative impact on patient survival (p < 0.001). CONCLUSIONS: In this study, development or progression of metastatic lung disease was not affected by long bone stabilization strategy. IM manipulation of metastatic long bone fractures therefore may not result in a clinically relevant increase in metastatic lung burden. The results of this study also suggest that lung metastasis within 6 months of surgery for metastatic long bone lesions is negatively associated with patient survival. LEVEL OF EVIDENCE: III, therapeutic study.
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Neoplasias Óseas , Fracturas Espontáneas , Neoplasias Pulmonares , Clavos Ortopédicos , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugía , Fracturas Espontáneas/diagnóstico por imagen , Fracturas Espontáneas/epidemiología , Fracturas Espontáneas/cirugía , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/cirugía , Masculino , Estudios RetrospectivosRESUMEN
Introduction: Soft tissue sarcomas (STS) are highly metastatic, connective-tissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS). Materials and Results: A single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation. Discussion: These data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas.
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Proteínas de la Membrana , Sarcoma , Neoplasias de los Tejidos Blandos , Animales , Ratones , Linfocitos Infiltrantes de Tumor , Macrófagos/patología , Sarcoma/patología , Microambiente TumoralRESUMEN
BACKGROUND: Patients undergoing a major orthopedic surgery for metastatic bone disease (MBD) are at high risk of developing venous thromboembolic (VTE) complications. Despite concerns, there is no consensus on the most effective strategy to prevent VTE in these patients. The purpose of this systematic review was to determine the VTE rate following the surgical management of MBD. METHODS: The databases MEDLINE, EMBASE, and CENTRAL were searched using keywords related to VTE and MBD requiring surgical management. Included studies reported VTE rates in patients with surgically managed MBD. Descriptive statistics and weighted mean totals were calculated. RESULTS: In total, 2082 abstracts were screened, and 29 studies were included. The overall VTE rate was 4.7%. Patients receiving surgery for impending pathologic fracture had a higher rate of VTE (5.6%) compared to patients with acute pathologic fractures (4.2%). Low-molecular-weight heparin was the most used chemoprophylaxis. CONCLUSIONS: Relative to other cancer and orthopedic patients, the VTE rate is extremely high in patients with MBD. The discordant recommendations of thromboprophylaxis, and absence of research in this distinct and more granular surgical oncology subgroup, underpins the challenges associated with developing guidelines to lessen the VTE risks in the MBD patient population.
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Neoplasias Óseas/complicaciones , Fijación de Fractura/efectos adversos , Fracturas Espontáneas/cirugía , Tromboembolia Venosa/etiología , Anticoagulantes/uso terapéutico , Neoplasias Óseas/secundario , Fracturas Espontáneas/etiología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Complicaciones Posoperatorias , Tromboembolia Venosa/prevención & controlRESUMEN
Sarcomas are rare, difficult to treat, mesenchymal lineage tumours that affect children and adults. Immunologically-based therapies have improved outcomes for numerous adult cancers, however, these therapeutic strategies have been minimally effective in sarcoma so far. Clinically relevant, immunologically-competent, and transplantable pre-clinical sarcoma models are essential to advance sarcoma immunology research. Herein we show that Cre-mediated activation of KrasG12D, and deletion of Trp53, in the hindlimb muscles of C57Bl/6 mice results in the highly penetrant, rapid onset undifferentiated pleomorphic sarcomas (UPS), one of the most common human sarcoma subtypes. Cell lines derived from spontaneous UPS tumours can be reproducibly transplanted into the hindlimbs or lungs of naïve, immune competent syngeneic mice. Immunological characterization of both spontaneous and transplanted UPS tumours demonstrates an immunologically-'quiescent' microenvironment, characterized by a paucity of lymphocytes, limited spontaneous adaptive immune pathways, and dense macrophage infiltrates. Macrophages are the dominant immune population in both spontaneous and transplanted UPS tumours, although compared to spontaneous tumours, transplanted tumours demonstrate increased spontaneous lymphocytic infiltrates. The growth of transplanted UPS tumours is unaffected by host lymphocyte deficiency, and despite strong expression of PD-1 on tumour infiltrating lymphocytes, tumours are resistant to immunological checkpoint blockade. This spontaneous and transplantable immune competent UPS model will be an important experimental tool in the pre-clinical development and evaluation of novel immunotherapeutic approaches for immunologically cold soft tissue sarcomas.
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Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias de los Músculos/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Sarcoma/genética , Proteína p53 Supresora de Tumor/genética , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Femenino , Miembro Posterior , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Linfocitos Infiltrantes de Tumor/inmunología , Macrófagos/inmunología , Masculino , Ratones , Ratones Transgénicos , Neoplasias de los Músculos/inmunología , Neoplasias de los Músculos/patología , Músculo Esquelético/patología , Mutación , Sarcoma/inmunología , Sarcoma/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
BACKGROUND: Patients undergoing an orthopedic surgery for bone or soft tissue sarcoma are at increased venous thromboembolism (VTE) risk. Unfortunately, there is a lack of thromboprophylaxis guidelines in this population. The purpose of this systematic review was to determine the soft tissue and bone sarcoma VTE rate and to explore the thromboprophylaxis regimens used. METHODS: The databases MEDLINE, EMBASE, and CENTRAL were queried using keywords related to VTE and long bone malignancy requiring surgical intervention to 2020. Included studied reported VTE rate in patients with surgically managed extremity sarcoma. Descriptive statistics and weighted mean totals were calculated. RESULTS: A total of 2082 studies were screened and 23 studies were included. The overall VTE rate was 2.9%, with a rate of 3.7% and 1.4% in patients with bone and soft tissue sarcomas, respectively. Low-molecular-weight heparin was the most commonly used chemoprophylaxis. CONCLUSIONS: There is a high VTE rate following sarcoma surgery. The VTE rate is higher in bone sarcoma surgery, which may be attributed to differences in surgery and postoperative recovery. There was no consensus on the duration or type of thromboprophylaxis used. Future research is needed to determine the most effective thromboprophylaxis regimen in patients with sarcoma and whether individualized thromboprophylaxis is required.
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Neoplasias Óseas/cirugía , Procedimientos Ortopédicos/estadística & datos numéricos , Osteosarcoma/cirugía , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Tromboembolia Venosa/epidemiología , Neoplasias Óseas/epidemiología , Neoplasias Óseas/patología , Estudios de Casos y Controles , Extremidades/patología , Extremidades/cirugía , Humanos , Estudios Observacionales como Asunto , Procedimientos Ortopédicos/efectos adversos , Osteosarcoma/epidemiología , Osteosarcoma/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Sarcoma/epidemiología , Neoplasias de los Tejidos Blandos/epidemiología , Neoplasias de los Tejidos Blandos/patología , Tromboembolia Venosa/etiologíaRESUMEN
BACKGROUND: There is a paucity of research examining how surgical decision-making for metastatic bone disease (MBD) can be optimized to improve quality of life (QOL) and functional outcomes, while accurately aligning with patient goals and expectations. The objective of this study was to survey and interview patients with MBD and support persons (PS), physicians, and allied health care providers (HCP) with the goal of identifying (1) important surgical issues related to MBD management, (2) discordance in perioperative expectations, and (3) perceived measures of success in the surgical management of MBD. METHODS: Utilizing a custom survey developed by HCP and patients with MBD, participants were asked to (1) identify important issues related to MBD management, (2) rank perceived measures of success, and (3) answer open-ended questions pertaining to the management of MBD. RESULTS: From the survey, increased life expectancy, minimizing disease progression, removal of local tumour, timely surgery after diagnosis, increased length of hospitalization, and physiotherapy access were all identified as significant discordant goals between PS and physicians/HCP. Conversely, there was an agreement between physicians and HCP who considered improved QOL and functional outcomes as most important goals. Structured homogenous-group workshops identified the need for (1) improved discussions of prognosis, surgical options, expectations, timelines, and resources, (2) the use of a care team "quarterback", and (3) an increased use of multi-disciplinary treatment planning. CONCLUSIONS: We feel this data highlights the importance of improved communication and coordination in treating patients with MBD. Further research evaluating how surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients.
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Neoplasias Óseas/cirugía , Calidad de Vida/psicología , Adulto , Anciano , Neoplasias Óseas/secundario , Toma de Decisiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Encuestas y CuestionariosRESUMEN
BACKGROUND: The putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent. QUESTIONS/PURPOSES: (1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma. METHODS: In this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H2O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation. RESULTS: Constitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm versus 1316 ± 387.4 mm, mean difference 1009 mm [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm versus 326.1 ± 72.8 mm, mean difference 326.1 mm [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10 ± 8.3x10 photons/s versus 9.3 x 10 ± 1.5 x 10 photons/s, mean difference 8.6 x 10 photons/s [95% CI 5.1 x 10 to 1.2 x 10]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm versus 1335 ± 102.7 mm, mean difference 840.3 mm [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions. CONCLUSIONS: As demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted. CLINICAL RELEVANCE: Our results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.
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Proteína Morfogenética Ósea 2/metabolismo , Neoplasias Óseas/metabolismo , Diferenciación Celular , Proliferación Celular , Osteoblastos/metabolismo , Osteosarcoma/metabolismo , Adolescente , Animales , Proteína Morfogenética Ósea 2/genética , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular , Niño , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Endogámicos C3H , Ratones Endogámicos NOD , Ratones SCID , Invasividad Neoplásica , Osteoblastos/patología , Osteosarcoma/genética , Osteosarcoma/patología , Transducción de Señal , Carga TumoralRESUMEN
CASE: A healthy 36-year-old man developed compartment syndrome of the posterior thigh with an associated sciatic nerve palsy secondary to an acute proximal hamstring tendon avulsion injury. CONCLUSION: Compartment syndrome of the thigh is rare and is usually associated with high-energy trauma. Atraumatic causes have been described, typically involving the anterior compartment. Posterior thigh compartment syndrome is especially uncommon. This case highlights the potential occurrence of posterior thigh compartment syndrome after proximal hamstring tendon rupture. Given the morbidity associated with compartment syndrome, it is important to recognize the risk factors and injury patterns that can cause thigh compartment syndrome.
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Síndromes Compartimentales/etiología , Fasciotomía , Tendones Isquiotibiales/lesiones , Traumatismos de los Tendones/complicaciones , Adulto , Síndromes Compartimentales/cirugía , Humanos , Masculino , Terapia de Presión Negativa para Heridas , Traumatismos de los Tendones/cirugíaRESUMEN
CASE: We present a case of acute disseminated intravascular coagulation (DIC) after prophylactic femoral intramedullary stabilization in a patient with metastatic prostate cancer. Preoperative international normalized ratio of 1.4 was attributed to malnutrition, and the patient was not medically optimized. DIC developed 1 hour postoperatively and was managed with blood product resuscitation. At the 4-month follow-up, the patient presented with bilateral pulmonary emboli and was transitioned to palliative care. CONCLUSIONS: DIC after intramedullary stabilization in patients with metastatic bone disease is a rare condition with high mortality rate. Early recognition, blood product resuscitation, and involvement of appropriate subspecialty services are imperative in DIC management.
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Neoplasias Óseas/cirugía , Coagulación Intravascular Diseminada/etiología , Fémur/cirugía , Fijación Intramedular de Fracturas/efectos adversos , Complicaciones Posoperatorias/etiología , Neoplasias de la Próstata/complicaciones , Anciano de 80 o más Años , Neoplasias Óseas/complicaciones , Neoplasias Óseas/secundario , Fémur/patología , Humanos , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
We report a polymer-based sensor that rapidly detects cancer based on changes in serum protein levels. Using three ratiometric fluorescence outputs, this simple system identifies early stage and metastatic lung cancer with a high level of accuracy exceeding many biomarker-based assays, making it an attractive strategy for point-of-care testing.
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Biomarcadores de Tumor/sangre , Proteínas Sanguíneas/análisis , Colorantes Fluorescentes/química , Neoplasias Pulmonares/diagnóstico por imagen , Polímeros/química , Animales , Fluorescencia , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/secundario , Ratones , Ratones Transgénicos , Estructura Molecular , Neoplasias Experimentales/sangre , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/secundario , Pruebas en el Punto de AtenciónRESUMEN
BACKGROUND: Management of metastatic bone disease of the extremities (MBD-E) is challenging, and surgical directions pose significant implications for overall patient morbidity and mortality. Recent literature reviews on the surgical management of MBD-E present a paucity of high-level evidence and global inconsistencies in study design. In order to steer productive research, a scoping review was performed to map and assess critical knowledge gaps. METHODS: The Arksey and O'Malley framework for scoping studies was followed. A comprehensive literature search identified a large body of literature pertaining to the surgical management of MBD-E. Study data and meta-data was extracted and presented using descriptive analytics and a thematic framework. Literature gaps were identified and analyzed. RESULTS: Three hundred eighty five studies from 1969 to 2017 were included. Studies were categorized into 11 separate themes, with the majority (63%) falling into the "surgical fixation strategies" theme, followed by "complications" at 7% and "prognosis and survival" at 6.2%. Less than 3% of studies were categorized in "patient related outcomes" or "epidemiology" themes. 89% of studies were retrospective and only 6 studies were of level 1 or 2 evidence. We identified a temporal increase in publication by decade, and all studies published on interventional radiology techniques or economic analyses were published after 2007 or 2009, respectively. 64.9% of studies were published in Europe and 20.3% were published in North America. Average patient age was 62 (± 5.2 years), and breast was the most common primary tumour (28%), followed by lung (17%) and kidney (15%). In terms of surgical location, 75% of operations involved the femur, followed by the humerus at 22% and tibia at 3%. CONCLUSIONS: We present a descriptive overview of the current published literature on the surgical management of MBD-E. Critical knowledge gaps have been identified through the development of a thematic framework. Consolidation of literary gaps must involve bolstered efforts towards patient and family-engaged research initiatives and assessment of patient-related surgical outcomes. Multi-disciplinary engagement in developing prospective research will also help guide evidence-based personalized practice for these patients. By building on existing comprehensive patient databases and registries, knowledge on survival and prognostic parameters can be greatly improved.
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Neoplasias Óseas/secundario , Neoplasias Óseas/cirugía , Procedimientos Ortopédicos , Anciano , Neoplasias Óseas/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/mortalidad , Resultado del TratamientoRESUMEN
Synovial sarcoma (SS) is initiated by a t(X;18) chromosomal translocation and resultant SS18-SSX fusion oncogene. Only a few SS cell lines exist. None has been compared to its source tumor. In order to compare matched tumor and cell line pairs, we performed RNAseq on 3 tumor/cell line pairs from a genetically engineered mouse model of SS, as well as 2 pairs from human SS tumors. Transcriptomes of mouse tumors and derivative cell lines deviated significantly. Differentially expressed genes highlighted inflammatory infiltrates and metabolism. The same was found for the human tumor and cell line pairs. More was shared between different tumors than between any tumor and its cell line. Direct xenografting generated transcriptomes that more closely resembled the primary tumor than did its derivative cell line. SS tumor transcriptomes are powerfully impacted by the environment wherein they reside, especially with regard to immune interaction and metabolism.
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OBJECTIVES: Mast cells have been identified as key mediators of posttraumatic joint contracture, and stabilizing medications (ketotifen) have been shown to decrease contracture severity. Serum mast cell tryptase (SMCT) levels are used clinically to monitor mast cell-mediated conditions. The goals of this study were to determine if SMCT levels are elevated in the setting of joint contracture, if they can be decreased in association with ketotifen therapy, and if they correlate with contracture severity. METHODS: This study used a previously developed rabbit model in which 39 animals were divided into 4 groups: operatively created joint contracture (ORC, n = 13), operatively created contracture treated with ketotifen at 2 doses (KF0.5, n = 9; KF1.0, n = 9), and healthy rabbits (NC, n = 8). Range of motion measures were performed at 8 weeks after the surgery. Serum samples were collected on postoperative days 1, 3, 5, 7, 21, 35, and 49. SMCT levels were measured using a rabbit-specific enzyme-linked immunosorbent assay. RESULTS: Levels of SMCT were highest in the operatively created joint contracture group and were significantly greater compared with both ketotifen groups (P < 0.001). Levels were highest at postoperative day 1 with a trend to decrease over time. A positive correlation between SMCT levels and contracture severity was observed in all operative groups (P < 0.05). CONCLUSIONS: Levels of SMCT are elevated in the setting of joint contracture, decreased in association with ketotifen therapy, and positively correlated with contracture severity. This is the first study to establish a relationship between SMCT and joint injury. Measurement of SMCT may be valuable in identifying those at risk of posttraumatic joint contracture.
Asunto(s)
Contractura/sangre , Contractura/diagnóstico , Traumatismos de la Rodilla/sangre , Traumatismos de la Rodilla/diagnóstico , Triptasas/sangre , Animales , Biomarcadores/sangre , Conejos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
ß-catenin is a master regulator in the cellular biology of development and neoplasia. Its dysregulation is implicated as a driver of colorectal carcinogenesis and the epithelial-mesenchymal transition in other cancers. Nuclear ß-catenin staining is a poor prognostic sign in synovial sarcoma, the most common soft-tissue sarcoma in adolescents and young adults. We show through genetic experiments in a mouse model that expression of a stabilized form of ß-catenin greatly enhances synovial sarcomagenesis. Stabilization of ß-catenin enables a stem-cell phenotype in synovial sarcoma cells, specifically blocking epithelial differentiation and driving invasion. ß-catenin achieves its reprogramming in part by upregulating transcription of TCF/LEF target genes. Even though synovial sarcoma is primarily a mesenchymal neoplasm, its progression towards a more aggressive and invasive phenotype parallels the epithelial-mesenchymal transition observed in epithelial cancers, where ß-catenin's transcriptional contribution includes blocking epithelial differentiation.