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Background: Percutaneous ankle fusion is an emerging technique with minimal published outcome data. The goal of the present study is to retrospectively review clinical and radiographic outcomes following percutaneous ankle fusion and provide technique tips to perform percutaneous ankle fusion. Methods: Patients >18 years of age, treated by a single surgeon, from February 2018 to June 2021, who underwent primary isolated percutaneous ankle fusion supplemented with platelet-derived growth factor B (rhPDGF-BB) and beta-tricalcium phosphate, with at least 1-year follow-up were included. Surgical technique consisted of percutaneous ankle preparation followed by fixation with 3 headless compression screws. Pre- and postoperative visual analog scale (VAS) and Foot Function Index (FFI) were compared using paired t tests. Fusion was assessed radiographically by the surgeon on postoperative radiographs and computed tomography (CT) at 3 months postoperatively. Results: Twenty-seven consecutive adult patients were included in the study. Mean follow-up was 21 months. Mean age was 59.8 years. Mean preoperative and postoperative VAS scores were 7.4 and 0.2, respectively (P < .01). Mean preoperative FFI pain domain, disability domain, activity restriction domain, and total score were 20.9, 16.7, 18.5, and 56.4, respectively. Mean postoperative FFI pain domain, disability domain, activity restriction domain, and total score were 4.3, 4.7, 6.7, and 15.8, respectively (P < .01). Fusion was achieved in 26 of 27 patients (96.3%) at 3 months. Four patients (14.8%) had complications. Conclusion: We found in this cohort with surgery performed by a surgeon highly experienced in minimally invasive surgery that percutaneous ankle fusion augmented with a bone graft supplement achieved a high rate of fusion (96.3%) and a significant improvement in pain and function postoperatively while associated with minimal complications. Level of Evidence: Level IV, case series.
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The ecancer Choosing Wisely conference was held for the second time in Africa in Dar es Salaam, Tanzania, from the 9th to 10th of February 2023. ecancer in collaboration with the Tanzania Oncology Society organised this conference which was attended by more than 150 local and international delegates. During the 2 days of the conference, more than ten speakers from different specialties in the field of oncology gave insights into Choosing Wisely in oncology. Topics from all fields linked to cancer care such as radiation oncology, medical oncology, prevention, oncological surgery, palliative care, patient advocacy, pathology, radiology, clinical trials, research and training were presented to share and bring awareness to professionals in oncology, on how to choose wisely in their approach to their daily practice, based on the available resources, while trying to offer the maximum benefit to the patient. This report, therefore, shares the highlights of this conference.
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INTRODUCTION: Appendicitis continues to be a common surgical emergency in children, but its diagnosis remains challenging. Use of diagnostic imaging to confirm appendicitis has gained popularity in some countries because it is associated with lower negative appendicectomy rates. This study reports our centre's experience of adopting routine ultrasound for the investigation of suspected appendicitis in children. METHODS: A single-centre retrospective cohort study was performed investigating all children aged 5-16 years admitted under surgeons with suspected appendicitis, in January-December 2019. Primary outcomes were the rate of ultrasound use, its accuracy in diagnosing/excluding appendicitis and negative appendicectomy rate. Other outcomes were treatment received, length of stay and complications. RESULTS: The majority of the 193 children with suspected appendicitis underwent a diagnostic ultrasound (87.5%). Ultrasound was highly sensitive (0.90, 95% confidence interval (CI) 0.81-0.96) and specific (1.0, 95% CI 0.96-1.0) for appendicitis in this study. Negative appendicectomy rate was extremely low (1.4%). Laparoscopic appendicectomy was the preferred management (75/86), with one case started open and no conversions to open. A minority of cases of simple appendicitis (10/86) were treated primarily with antibiotics. Rates of complex appendicitis and postoperative complications were similar to other studies. CONCLUSION: Ultrasound can be highly sensitive and specific for appendicitis. Its routine use to confirm appendicitis prior to surgery is associated with a low negative appendicectomy rate. This is a major change in practice for a general surgical unit in the United Kingdom.
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Apendicite , Laparoscopia , Humanos , Criança , Apendicite/diagnóstico por imagem , Apendicite/cirurgia , Estudos Retrospectivos , Laparoscopia/métodos , Apendicectomia/métodos , UltrassonografiaRESUMO
Particulate matter (PM) concentration levels in the London Underground (LU) are higher than London background levels and beyond World Health Organization (WHO) defined limits. Wheel, track, and brake abrasion are the primary sources of particulate matter, producing predominantly Fe-rich particles that make the LU microenvironment particularly well suited to study using environmental magnetism. Here we combine magnetic properties, high-resolution electron microscopy, and electron tomography to characterize the structure, chemistry, and morphometric properties of LU particles in three dimensions with nanoscale resolution. Our findings show that LU PM is dominated by 5-500 nm particles of maghemite, occurring as 0.1-2 µm aggregated clusters, skewing the size-fractioned concentration of PM artificially to larger sizes when measured with traditional monitors. Magnetic properties are largely independent of the PM filter size (PM10, PM4, and PM2.5), and demonstrate the presence of superparamagnetic (< 30 nm), single-domain (30-70 nm), and vortex/pseudo-single domain (70-700 nm) signals only (i.e., no multi-domain particles > 1 µm). The oxidized nature of the particles suggests that PM exposure in the LU is dominated by resuspension of aged dust particles relative to freshly abraded, metallic particles from the wheel/track/brake system, suggesting that periodic removal of accumulated dust from underground tunnels might provide a cost-effective strategy for reducing exposure. The abundance of ultrafine particles identified here could have particularly adverse health impacts as their smaller size makes it possible to pass from lungs to the blood stream. Magnetic methods are shown to provide an accurate assessment of ultrafine PM characteristics, providing a robust route to monitoring, and potentially mitigating this hazard.
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Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Londres , Material Particulado/análise , Poeira/análise , Nanopartículas Magnéticas de Óxido de Ferro , Fenômenos Magnéticos , Monitoramento Ambiental/métodos , Tamanho da PartículaRESUMO
Background: Some have suggested the use of generic surgical implants to curb rising costs of orthopaedic care. However, there is evidence that patients are reluctant to use generic pharmaceuticals as compared to their brand name equivalents for fear of inferior quality. Public perception of the use of generic implants remains unknown. Methods: We conducted a cross-sectional survey using Amazon MTurk to identify factors associated with a consumer preference for generic orthopaedic screws and total hip. Results: While much of the public (52%) sees the value of generic implants, fewer (26%) would prefer them in their own care. Most respondents (75%) trust their surgeon's choice, yet the vast majority (83%) want to be informed about the cost of their implant, even if it makes no difference in what they pay. The agreement that older implants are safer than newer implants (OR 1.9 for screws; 2.5 for hip arthroplasty), and that generics are a better value than brand name implants (OR 3.0 for screws; 4.3 for hip arthroplasty) were independently associated with a preference for generics. Conclusion: The observation that many people view generic implants as being a good value, yet fewer would prefer to use them in their own care indicates that concerns over quality may initially limit utilization of generic implants. More evidence is needed to reassure most consumers of the safety and effectiveness of generic implants. Additionally, our findings demonstrate a desire for more implant price transparency when undergoing orthopaedic surgery.
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SUMMARY: Several surgical procedures have been described to treat thumb carpometacarpal osteoarthritis, including suture button suspensionplasty and ligament reconstruction and tendon interposition. To date, no single procedure has demonstrated clinical superiority. Suture button suspensionplasty has achieved favorable outcomes at 5 years in primary cases, but has not been validated in revision surgery. In this study, it was evaluated for revision of failed thumb carpometacarpal osteoarthritis surgery, and outcomes were compared to ligament reconstruction and tendon interposition outcomes. A retrospective chart review identified patients who underwent suture button suspensionplasty or ligament reconstruction and tendon interposition after failure of previous thumb carpometacarpal osteoarthritis surgery since 2010. Eighteen patients were included, with nine patients in each group. Eighteen patients had mean final follow-up of 35 months. There were two complications in the ligament reconstruction and tendon interposition group and none in the suture button suspensionplasty group. No patients required additional surgery. The suture button suspensionplasty group had an average visual analogue scale pain score improvement of 2.9, compared to 2.4 in the ligament reconstruction and tendon interposition group. Average final Quick Disabilities of the Arms, Shoulder and Hand questionnaire score was 15.1 in the suture button suspensionplasty group, compared to 22.6 in the ligament reconstruction and tendon interposition group. Mean operative time of 86.3 minutes in the suture button suspensionplasty group was significantly shorter than the 121-minute mean in the ligament reconstruction and tendon interposition group. Suture button suspensionplasty is an effective treatment option for revision of previous thumb carpometacarpal osteoarthritis surgery, with outcomes comparable to revision using ligament reconstruction and tendon interposition, and the added benefit of shorter operative times and early mobilization. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
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Articulações Carpometacarpais , Osteoartrite , Trapézio , Articulações Carpometacarpais/cirurgia , Humanos , Ligamentos/cirurgia , Osteoartrite/cirurgia , Reoperação , Estudos Retrospectivos , Suturas , Tendões/cirurgia , Polegar/cirurgia , Trapézio/cirurgiaRESUMO
BACKGROUND: Little is known about the drivers of readmission in patients undergoing Orthopaedic oncologic resection. The goal of this study was to identify factors independently associated with 90-day readmission for patients undergoing oncologic resection and subsequent prosthetic reconstruction for primary tumors involving bone. METHODS: This was a retrospective comparative cohort study of patients treated from 2008 to 2019 who underwent endoprosthetic reconstruction for a primary bone tumor or soft tissue tumor involving bone, as well as those who underwent a revision endoprosthetic reconstruction if the primary endoprosthetic reconstruction was performed for an oncologic resection. The primary outcome measure was unplanned 90-day readmission. RESULTS: A total of 149 patients were identified who underwent 191 surgeries were for a primary bone or soft tissue tumor. The 90-day readmission rate was 28.3%. Female gender, depression, higher tumor grade, vascular reconstruction, longer procedure duration, longer length of stay (LOS), multiple surgeries during an admission and disposition to a Skilled Nursing Facility were associated with readmission (p < 0.05). In a multivariate analysis, female sex, higher tumor grade and longer procedure duration were independently associated with risk of readmission (p < 0.05). CONCLUSIONS: Readmission rates are high following endoprosthetic reconstruction for Orthopaedic oncologic resections. Further work is necessary to help minimize unplanned readmissions.
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Neoplasias Ósseas , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Estudos de Coortes , Feminino , Humanos , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgiaRESUMO
BACKGROUND: Orthopedic oncology patients are particularly susceptible to increased readmission rates and poor surgical outcomes, yet little is known about readmission rates. The goal of this study is to identify factors independently associated with 90-day readmission for patients undergoing oncologic resection and subsequent prosthetic reconstruction for metastatic disease of the hip and knee. METHODS: This is a retrospective comparative cohort study of all patients treated from 2013 to 2019 at a single tertiary care referral institution who underwent endoprosthetic reconstruction by an orthopedic oncologist for metastatic disease of the extremities. The primary outcome measure was unplanned 90-day readmission. RESULTS: We identified 112 patients undergoing 127 endoprosthetic reconstruction surgeries. Metastatic disease was most commonly from renal (26.8%), lung (23.6%), and breast (13.4%) cancer. The most common type of skeletal reconstruction performed was simple arthroplasty (54%). There were 43 readmissions overall (33.9%). When controlling for confounding factors, body mass index >40, insurance status, peripheral vascular disease, and longer hospital length of stay were independently associated with risk of readmission (P ≤ .05). CONCLUSION: Readmission rates for endoprosthetic reconstructions for metastatic disease are high. Although predicting readmission remains challenging, risk stratification presents a viable option for helping minimize unplanned readmissions. LEVEL OF EVIDENCE: III.
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Neoplasias , Readmissão do Paciente , Estudos de Coortes , Humanos , Extremidade Inferior , Neoplasias/epidemiologia , Neoplasias/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Unlike other soft tissue sarcomas, atypical lipomatous tumors (ALTs) are thought to have a low propensity for metastasis. Despite this, a standard of care for pulmonary metastasis (PM) surveillance has not been established. This study aimed to evaluate the utility of chest imaging for PM surveillance following ALT excision. METHODS: This was a multi-institution, retrospective review of all patients with primary ALTs of the extremities or superficial torso who underwent excision between 2006 and 2018. Minimum follow-up was two years. Long-term survival was evaluated using the Kaplan-Meier method. RESULTS: 190 patients with ALT were included. Average age was 61.7 years and average follow-up was 58.6 months (24 to 180 months). MDM2 testing was positive in 88 patients (46.3%), and 102 (53.7%) did not receive MDM2 testing. 188 patients (98.9%) had marginal excision, and 127 (66.8%) had marginal or positive margins. Patients received an average of 0.9 CT scans and 1.3 chest radiographs over the surveillance period. 10-year metastasis-free survival was 100%, with no documented deaths from disease. CONCLUSIONS: This study suggests that chest imaging does not have a significant role in PM surveillance following ALT excision, but advanced local imaging and chest surveillance may be considered in cases of local recurrence or concern for dedifferentiation.
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Carcinoma Epitelial do Ovário/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Estudos Multicêntricos como Assunto , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: In recent years, there has been growing interest in the use of reverse total shoulder arthroplasty (rTSA) for reconstruction of the proximal humerus after oncologic resection. However, the indications and outcomes of oncologic rTSA remain unclear. METHODS: We conducted a systematic review to identify studies that reported outcomes of patients who underwent rTSA for oncologic reconstruction of the proximal humerus. Extracted data included demographic characteristics, indications, operative techniques, outcomes, and complications. Weighted means were calculated according to sample size. RESULTS: Twelve studies were included, containing 194 patients who underwent rTSA for oncologic reconstruction of the proximal humerus. The mean patient age was 48 years, and 52% of patients were male. Primary malignancies were present in 55% of patients; metastatic disease, 30%; and benign tumors, 9%. The mean humeral resection length was 12 cm. The mean postoperative Musculoskeletal Tumor Society score was 78%; Constant score, 60; and Toronto Extremity Salvage Score, 77%. The mean complication rate was 28%, with shoulder instability accounting for 63% of complications. Revisions were performed in 16% of patients, and the mean implant survival rate was 89% at a mean follow-up across studies of 53 months. CONCLUSIONS: Although the existing literature is of poor study quality, with a high level of heterogeneity and risk of bias, rTSA appears to be a suitable option in appropriately selected patients undergoing oncologic resection and reconstruction of the proximal humerus. The most common complication is instability. Higher-quality evidence is needed to help guide decision making on appropriate implant utilization for patients undergoing oncologic resection of the proximal humerus.
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Artroplastia do Ombro , Instabilidade Articular , Articulação do Ombro , Humanos , Úmero/cirurgia , Instabilidade Articular/cirurgia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos , Ombro , Articulação do Ombro/cirurgia , Resultado do TratamentoRESUMO
Since 2012, the European Radiation Dosimetry Group (EURADOS) has developed its Strategic Research Agenda (SRA), which contributes to the identification of future research needs in radiation dosimetry in Europe. Continued scientific developments in this field necessitate regular updates and, consequently, this paper summarises the latest revision of the SRA, with input regarding the state of the art and vision for the future contributed by EURADOS Working Groups and through a stakeholder workshop. Five visions define key issues in dosimetry research that are considered important over at least the next decade. They include scientific objectives and developments in (i) updated fundamental dose concepts and quantities, (ii) improved radiation risk estimates deduced from epidemiological cohorts, (iii) efficient dose assessment for radiological emergencies, (iv) integrated personalised dosimetry in medical applications and (v) improved radiation protection of workers and the public. This SRA will be used as a guideline for future activities of EURADOS Working Groups but can also be used as guidance for research in radiation dosimetry by the wider community. It will also be used as input for a general European research roadmap for radiation protection, following similar previous contributions to the European Joint Programme for the Integration of Radiation Protection Research, under the Horizon 2020 programme (CONCERT). The full version of the SRA is available as a EURADOS report (www.eurados.org).
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Monitoramento de Radiação , Proteção Radiológica , Europa (Continente) , Humanos , Doses de Radiação , Radiação Ionizante , RadiometriaRESUMO
The lack of mailed dosimetry audits of proton therapy centres in Europe has encouraged researchers of EURADOS Working Group 9 (WG9) to compare response of several existing passive detector systems in therapeutic pencil beam scanning. Alanine Electron Paramagnetic Resonance dosimetry systems from 3 different institutes (ISS, Italy; UH, Belgium and IFJ PAN, Poland), natLiF:Mg, Ti (MTS-N) and natLiF:Mg, Cu, P (MCP-N) thermoluminescent dosimeters (TLDs), GD-352M radiophotoluminescent glass dosimeters (RPLGDs) and Al2O3:C optically stimulated dosimeters (OSLDs) were evaluate. Dosimeter repeatability, batch reproducibility and response in therapeutic Pencil Beam Scanning were verified for implementation as mail auditing system. Alanine detectors demonstrated the lowest linear energy transfer (LET) dependence with an agreement between measured and treatment planning system (TPS) dose below 1%. The OSLDs measured on average a 6.3% lower dose compared to TPS calculation, with no significant difference between varying modulations and ranges. Both GD-352M and MCP-N measured a lower dose than the TPS and luminescent response was dependent on the LET of the therapeutic proton beam. Thermoluminescent response of MTS-N was also found to be dependent on the LET and a higher dose than TPS was measured with the most pronounced increase of 11%. As alanine detectors are characterized by the lowest energy dependence for different parameters of therapeutic pencil beam scanning they are suitable candidates for mail auditing in proton therapy. The response of luminescence detector systems have shown promises even though more careful calibration and corrections are needed for its implementation as part of a mailed dosimetry audit system.
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Terapia com Prótons , Bélgica , Europa (Continente) , Itália , Polônia , Prótons , Dosímetros de Radiação , Radiometria , Reprodutibilidade dos Testes , Dosimetria TermoluminescenteRESUMO
CASE: A 72-year-old man underwent intramedullary nailing of a humeral diaphysis fracture with passage through an unrecognized pathologic fracture. Four months later, a biopsy of a soft-tissue mass in the arm revealed pleomorphic undifferentiated sarcoma. Only after local recurrence and forequarter amputation was the story of a pathologic fracture through undifferentiated pleomorphic sarcomas of bone clear. The patient developed metastatic disease and died after 2 years postoperatively. DISCUSSION: Orthopaedic surgeons should consider sarcoma when assessing patients with fractures of unknown etiology and an inappropriate mechanism because the placement of an intramedullary device through a sarcoma of bone has consequences.
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Fixação Intramedular de Fraturas , Fraturas do Úmero , Sarcoma , Idoso , Pinos Ortopédicos/efeitos adversos , Fixação Intramedular de Fraturas/efeitos adversos , Humanos , Fraturas do Úmero/diagnóstico por imagem , Úmero/diagnóstico por imagem , Masculino , Recidiva Local de Neoplasia , Sarcoma/diagnóstico por imagemRESUMO
OBJECTIVE: We describe a novel educational model for a student-led anatomy interest group that utilizes an efficient method of knowledge sharing among peers in order to supplement the standard gross anatomy curriculum and expose medical students to advanced, surgically relevant anatomy. DESIGN: Student leaders of the Advanced Anatomy Interest Group compile a list of advanced anatomy "tidbits" related to a topic within a particular surgical specialty. Each medical student participant signs up for a different "tidbit" and prepares a short presentation. On meeting day, students present to the group. After each presentation, a surgical faculty moderator offers feedback and provides additional surgical perspective. SETTING: Duke University School of Medicine, Durham, NC, USA. PARTICIPANTS: Three third year medical student interest group leaders, 20 first through fourth year medical student participants, and 1 surgical faculty moderator. RESULTS: Twelve students presented an advanced anatomy tidbit, and 15 students responded to a 10-question postmeeting survey. Over 90% of respondents either agreed or strongly agreed that their understanding of surgically relevant anatomy had improved. Of those students who presented, 100% agreed or strongly agreed that their preparedness to briefly teach complex medical topics to colleagues had improved. Additionally, students reported increased interest in surgery and an improved perception of surgeons. CONCLUSIONS: This novel educational model appears to be an effective and efficient way to supplement the standard gross anatomy curriculum and expose medical students to advanced, surgically relevant anatomy. In addition, this model enables students to hone their presentation skills, gain experience teaching advanced medical concepts to peers, and develop relationships with surgical faculty. Surgical faculty are also not burdened with any preparatory responsibilities, making their participation more feasible. This model can serve as a template for medical students, house staff, and faculty interested in expanding anatomy education at their own institutions.
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Anatomia , Educação de Graduação em Medicina , Internato e Residência , Estudantes de Medicina , Anatomia/educação , Currículo , Humanos , Modelos Educacionais , Grupo Associado , EnsinoRESUMO
Vascularized composite allografts (VCAs) can restore fully functional anatomic units in patients with limb amputations or severe facial tissue loss. However, acute rejection of the skin is frequently observed and underscores the importance of developing tolerance induction protocols. In this study, we have characterized the skin immune system in VCAs. We demonstrate infiltration of recipient leukocytes, regardless of rejection status, and in tolerant mixed hematopoietic chimeras, the co-existence of these cells with donor leukocytes in the absence of rejection. Here we characterize the dermal T cell and epidermal Langerhans cell components of the skin immune system in our porcine model of VCA tolerance, and the kinetics of cutaneous chimerism in both of these populations in VCAs transplanted to tolerant and nontolerant recipients, as well as in host skin. Furthermore, in biopsies from the first patient to receive a hand transplant in our program, we demonstrate the presence of recipient T cells in the skin of the transplanted limb in the absence of clinical or histological evidence of rejection.
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Aloenxertos Compostos , Animais , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Leucócitos , Suínos , Quimeras de TransplanteRESUMO
The lowest possible energy of proton scanning beam in cyclotron proton therapy facilities is typically between 60 and 100 MeV. Treatment of superficial lesions requires a pre-absorber to deliver doses to shallower volumes. In most of the cases a range shifter (RS) is used, but as an alternative solution, a patient-specific 3D printed proton beam compensator (BC) can be applied. A BC enables further reduction of the air gap and consequently reduction of beam scattering. Such pre-absorbers are additional sources of secondary radiation. The aim of this work was the comparison of RS and BC with respect to out-of-field doses for a simulated treatment of superficial paediatric brain tumours. EURADOS WG9 performed comparative measurements of scattered radiation in the Proteus C-235 IBA facility (Cyclotron Centre Bronowice at the Institute of Nuclear Physics, CCB IFJ PAN, Kraków, Poland) using two anthropomorphic phantoms-5 and 10 yr old-for a superficial target in the brain. Both active detectors located inside the therapy room, and passive detectors placed inside the phantoms were used. Measurements were supplemented by Monte Carlo simulation of the radiation transport. For the applied 3D printed pre-absorbers, out-of-field doses from both secondary photons and neutrons were lower than for RS. Measurements with active environmental dosimeters at five positions inside the therapy room indicated that the RS/BC ratio of the out-of-field dose was also higher than one, with a maximum of 1.7. Photon dose inside phantoms leads to higher out-of-field doses for RS than BC to almost all organs with the highest RS/BC ratio 12.5 and 13.2 for breasts for 5 and 10 yr old phantoms, respectively. For organs closest to the isocentre such as the thyroid, neutron doses were lower for BC than RS due to neutrons moderation in the target volume, but for more distant organs like bladder-conversely-lower doses for RS than BC were observed. The use of 3D printed BC as the pre-absorber placed in the near vicinity of patient in the treatment of superficial tumours does not result in the increase of secondary radiation compared to the treatment with RS, placed far from the patient.
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Impressão Tridimensional , Terapia com Prótons/instrumentação , Doses de Radiação , Neoplasias Encefálicas/radioterapia , Criança , Simulação por Computador , Humanos , Método de Monte Carlo , Nêutrons , Imagens de Fantasmas , Dosagem RadioterapêuticaRESUMO
BACKGROUND/AIM: Inhibition of apoptosis is one of the hallmarks of cancer, and anti-apoptotic genes are often targets of genetic and epigenetic alterations. Cellular inhibitor of apoptosis 2 (cIAP2) has a role in degrading caspases by linking them to ubiquitin molecules, and is upregulated in triple-negative breast cancer (TNBC). Previous studies have demonstrated that cIAP2 may play a role in the epithelial-to-mesenchymal transition (EMT). MATERIALS AND METHODS: Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was administered to triple-negative breast cancer (TNBC) cells alone or in combination with epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor isolated from green tea. RESULTS: The compounds were able to decrease the expression of cIAP2 while increasing the expression of pro-apoptotic caspase 7. There were also changes in histone modifications, suggesting a role of epigenetic mechanisms in these changes in expression of cIAP2. These changes resulted in an increase in apoptosis. SAHA and EGCG were also capable of limiting TNBC cell migration across a fibronectin (FN) matrix. CONCLUSION: SAHA and EGCG reduce the metastatic potential of TNBC by inducing the apoptotic pathway.