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Current graft evaluation during normothermic ex situ liver perfusion lacks real-time parameters for predicting posttransplant hepatocyte and biliary function. Indocyanine green (ICG) imaging has been widely used in liver surgery, enabling the visualization of hepatic uptake and excretion through bile using near-infrared light. In this research, porcine livers under various ischemic conditions were examined during a 5-hour normothermic ex situ liver perfusion procedure, introducing ICG at 1 hour through the hepatic artery. These conditions included livers from heart-beating donors, donation after circulatory death (DCD) with warm ischemic durations of 60 minutes (DCD60) and 120 minutes (DCD120), as well as interventions utilizing tissue plasminogen activator in DCD120 cases (each n = 5). Distinct hepatic fluorescence patterns correlated with different degrees of ischemic injury ( p = 0.01). Low ICG uptake in the parenchyma (less than 40% of maximum intensity) was more prevalent in DCD120 (21.4%) compared to heart-beating donors (6.2%, p = 0.06) and DCD60 (3.0%, p = 0.02). Moreover, ICG clearance from 60 minutes to 240 minutes was significantly higher in heart-beating donors (69.3%) than in DCD60 (17.5%, p < 0.001) and DCD120 (32.1%, p = 0.01). Furthermore, thrombolytic intervention using tissue plasminogen activator in DCD120 resulted in noteworthy outcomes, including significantly reduced ALP levels ( p = 0.04) and improved ICG clearance ( p = 0.02) with a trend toward mitigating fibrin deposition similar to DCD60, as well as enhancements in bile production ( p = 0.09). In conclusion, ICG fluorescence imaging during normothermic ex situ liver perfusion provides real-time classification of hepatic vascular and biliary injuries, offering valuable insights for the more accurate selection and postintervention evaluation of marginal livers in transplantation.
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Verde de Indocianina , Trasplante de Hígado , Hígado , Perfusión , Animales , Verde de Indocianina/administración & dosificación , Trasplante de Hígado/métodos , Trasplante de Hígado/efectos adversos , Hígado/irrigación sanguínea , Hígado/cirugía , Hígado/diagnóstico por imagen , Perfusión/métodos , Porcinos , Isquemia Tibia/efectos adversos , Preservación de Órganos/métodos , Imagen Óptica/métodos , Fluorescencia , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/cirugíaRESUMEN
BACKGROUND: Joint-sparing resection of periarticular bone tumors can be challenging because of complex geometry. Successful reconstruction of periarticular bone defects after tumor resection is often performed with structural allografts to allow for joint preservation. However, achieving a size-matched allograft to fill the defect can be challenging because allograft sizes vary, they do not always match a patient's anatomy, and cutting the allograft to perfectly fit the defect is demanding. QUESTIONS/PURPOSES: (1) Is there a difference in mental workload among the freehand, patient-specific instrumentation, and surgical navigation approaches? (2) Is there a difference in conformance (quantitative measure of deviation from the ideal bone graft), elapsed time during reconstruction, and qualitative assessment of goodness-of-fit of the allograft reconstruction among the approaches? METHODS: Seven surgeons used three modalities in the same order (freehand, patient-specific instrumentation, and surgical navigation) to fashion synthetic bone to reconstruct a standardized bone defect. National Aeronautics and Space Administration (NASA) mental task load index questionnaires and procedure time were captured. Cone-beam CT images of the shaped allografts were used to measure conformance (quantitative measure of deviation from the ideal bone graft) to a computer-generated ideal bone graft model. Six additional (senior) surgeons blinded to modality scored the quality of fit of the allografts into the standardized tumor defect using a 10-point Likert scale. We measured conformance using the root-mean-square metric in mm and used ANOVA for multipaired comparisons (p < 0.05 was significant). RESULTS: There was no difference in mental NASA total task load scores among the freehand, patient-specific instrumentation, and surgical navigation techniques. We found no difference in conformance root-mean-square values (mean ± SD) between surgical navigation (2 ± 0 mm; mean values have been rounded to whole numbers) and patient-specific instrumentation (2 ± 1 mm), but both showed a small improvement compared with the freehand approach (3 ± 1 mm). For freehand versus surgical navigation, the mean difference was 1 mm (95% confidence interval [CI] 0.5 to 1.1; p = 0.01). For freehand versus patient-specific instrumentation, the mean difference was 1 mm (95% CI -0.1 to 0.9; p = 0.02). For patient-specific instrumentation versus surgical navigation, the mean difference was 0 mm (95% CI -0.5 to 0.2; p = 0.82). In evaluating the goodness of fit of the shaped grafts, we found no clinically important difference between surgical navigation (median [IQR] 7 [6 to 8]) and patient-specific instrumentation (median 6 [5 to 7.8]), although both techniques had higher scores than the freehand technique did (median 3 [2 to 4]). For freehand versus surgical navigation, the difference of medians was 4 (p < 0.001). For freehand versus patient-specific instrumentation, the difference of medians was 3 (p < 0.001). For patient-specific instrumentation versus surgical navigation, the difference of medians was 1 (p = 0.03). The mean ± procedural times for freehand was 16 ± 10 minutes, patient-specific instrumentation was 14 ± 9 minutes, and surgical navigation techniques was 24 ± 8 minutes. We found no differences in procedures times across three shaping modalities (freehand versus patient-specific instrumentation: mean difference 2 minutes [95% CI 0 to 7]; p = 0.92; freehand versus surgical navigation: mean difference 8 minutes [95% CI 0 to 20]; p = 0.23; patient-specific instrumentation versus surgical navigation: mean difference 10 minutes [95% CI 1 to 19]; p = 0.12). CONCLUSION: Based on surgical simulation to reconstruct a standardized periarticular bone defect after tumor resection, we found a possible small advantage to surgical navigation over patient-specific instrumentation based on qualitative fit, but both techniques provided slightly better conformance of the shaped graft for fit into the standardized post-tumor resection bone defect than the freehand technique did. To determine whether these differences are clinically meaningful requires further study. The surgical navigation system presented here is a product of laboratory research development, and although not ready to be widely deployed for clinical practice, it is currently being used in a research operating room setting for patient care. This new technology is associated with a learning curve, capital costs, and potential risk. The reported preliminary results are based on a preclinical synthetic bone tumor study, which is not as realistic as actual surgical scenarios. CLINICAL RELEVANCE: Surgical navigation systems are an emerging technology in orthopaedic and reconstruction surgery, and understanding their capabilities and limitations is paramount for clinical practice. Given our preliminary findings in a small cohort study with one scenario of standardized synthetic periarticular bone tumor defects, future investigations should include different surgical scenarios using allograft and cadaveric specimens in a more realistic surgical setting.
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Indocyanine green (ICG) is the only near-infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano-dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J-aggregation of ICG-dimer, resulting in a narrow, red-shifted (780â nmâ894â nm) and intense (≈2-fold) absorbance. Compared to ICG, Nano-dICG demonstrated superior photothermal conversion (2-fold higher), significantly reduced photodegradation (-9.6 % vs. -46.3 %), and undiminished photothermal effect (7 vs. 2â cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano-dICG enabled real-time tracking of its delivery to mouse tumors within 24â h by photoacoustic imaging at NIR wavelength (890â nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure-driven ICG dimerization leads to an ultra-stable phototheranostic platform.
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Nanopartículas , Nanoestructuras , Ratones , Animales , Verde de Indocianina/química , Dimerización , Nanopartículas/química , Nanoestructuras/uso terapéutico , Nanoestructuras/química , Polímeros , Fototerapia/métodos , Línea Celular TumoralRESUMEN
A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated.
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Polímeros , Andamios del Tejido , Regeneración Ósea , Huesos , Poliésteres/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
BACKGROUND: Monitoring circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), known as liquid biopsies, continue to be developed as diagnostic and prognostic markers for a wide variety of cancer indications, mainly due to their minimally invasive nature and ability to offer a wide range of phenotypic and genetic information. While liquid biopsies maintain significant promising benefits, there is still limited information regarding the kinetics of ctDNA and CTCs following radiation therapy which remains a vital treatment modality in head and neck cancers. This study aims to describe the kinetics of ctDNA and CTCs following radiation exposure in a preclinical rabbit model with VX2 induced buccal carcinoma. METHODS: Seven rabbits were inoculated with VX2 cells in the buccal mucosa and subjected to radiation. At selected time points, blood sampling was performed to monitor differing levels of ctDNA and CTC. Plasma ctDNA was measured with quantitative PCR for papillomavirus E6 while CTCs were quantified using an immunomagnetic nanoparticles within a microfluidic device. Comparisons of CTC detection with EpCAM compared to multiple surface markers (EGFR, HER2 and PSMA) was evaluated and correlated with the tumor size. RESULTS: Plasma ctDNA reflects the overall tumor burden within the animal model. Analysis of correlations between ctDNA with tumor and lymph node volumes showed a positive correlation (R = 0.452 and R = 0.433 [p < 0.05]), respectively. Over the course of treatment, ctDNA levels declined and quickly becomes undetectable following tumor eradication. While during the course of treatment, ctDNA levels were noted to rise particularly upon initiation of radiation following scheduled treatment breaks. Levels of CTCs were observed to increase 1 week following inoculation of tumor to the primary site. For CTC detection, the use of multiple surface markers showed a greater sensitivity when compared to detection using only EpCAM. Plasma CTC levels remained elevated following radiation therapy which may account for an increased shedding of CTCs following radiation. CONCLUSION: This study demonstrates the utility of ctDNA and CTCs detection in response to radiation treatment in a preclinical head and neck model, allowing for better understanding of liquid biopsy applications in both clinical practice and research development.
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Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/radioterapia , Ácidos Nucleicos Libres de Células/sangre , Neoplasias de la Boca/sangre , Neoplasias de la Boca/radioterapia , Animales , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/inducido químicamente , ADN Tumoral Circulante/sangre , Papillomavirus del Conejo de Rabo Blanco , Molécula de Adhesión Celular Epitelial/sangre , Neoplasias de Cabeza y Cuello/sangre , Neoplasias de Cabeza y Cuello/inducido químicamente , Neoplasias de Cabeza y Cuello/radioterapia , Separación Inmunomagnética/métodos , Biopsia Líquida/métodos , Masculino , Neoplasias de la Boca/inducido químicamente , Neoplasias de la Boca/virología , Nanopartículas , Trasplante de Neoplasias , Sistemas de Lectura Abierta , Conejos , Dosificación Radioterapéutica , Carga TumoralRESUMEN
BACKGROUND: Current sentinel lymph node biopsy (SLNB) techniques, including use of radioisotopes, have disadvantages including the use of a radioactive tracer. Indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging and cone beam CT (CBCT) have advantages for intraoperative use. However, limited literature exists regarding their use in head and neck cancer SLNB. METHODS: This was a prospective, non-randomized study using a rabbit oral cavity VX2 squamous cell carcinoma model (n = 10) which develops lymph node metastasis. Pre-operatively, images were acquired by MicroCT. During surgery, CBCT and NIR fluorescence imaging of ICG was used to map and guide the SLNB resection. RESULTS: Intraoperative use of ICG to guide fluorescence resection resulted in identification of all lymph nodes identified by pre-operative CT. CBCT was useful for near real time intraoperative imaging and 3D reconstruction. CONCLUSIONS: This pre-clinical study further demonstrates the technical feasibility, limitations and advantages of intraoperative NIR-guided ICG imaging for SLN identification as a complementary method during head and neck surgery.
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Tomografía Computarizada de Haz Cónico/métodos , Verde de Indocianina/administración & dosificación , Metástasis Linfática/diagnóstico por imagen , Neoplasias de la Boca/cirugía , Imagen Óptica/métodos , Ganglio Linfático Centinela/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Animales , Línea Celular Tumoral , Estudios de Factibilidad , Humanos , Masculino , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/patología , Trasplante de Neoplasias , Estudios Prospectivos , Conejos , Radiografía Intervencional , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático Centinela , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Microtomografía por Rayos XRESUMEN
BACKGROUND: Surgical precision in the reconstruction of the orbital floor is crucial to functional visual and aesthetic outcomes. Increasingly, computer-aided design is being utilized to aid in precise preoperative planning by using the mirror images of the unaffected side. The authors aim to use 3-dimensional (3D) quantitative analysis to establish whether the native orbital floor topography is sufficiently symmetric to support this practice. METHODS: Ten high resolution head and neck computed tomography scans of patients without periorbital pathology were obtained. These were imported into a 3D medical image processing software and segmented to isolate bilateral orbital floors. Each native orbital floor was compared to the mirror image of the contralateral side by conformance map computation. Data collection included measures of 25% and 75% quartile, median, mean, standard deviation, and root-mean-square (RMS). RESULTS: The topographic analysis demonstrated a high degree of topographic conformance with a mean RMS of 0.58â±â0.37âmm. Further volumetric analysis comparing the total orbital volume between each side also demonstrates a high degree of volumetric symmetry with a mean difference of 0.55âmL (Pâ=â0.30). CONCLUSION: Comparison of the native orbital floor and the mirror image of the contralateral side by conformance map computation and volumetric analysis demonstrated a high degree of morphologic similarity. The native orbital floor topography provides optimal symmetry to support mirror imaging techniques used in orbital floor reconstruction.
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Órbita/diagnóstico por imagen , Órbita/cirugía , Diseño Asistido por Computadora , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Procedimientos de Cirugía Plástica/métodos , Programas Informáticos , Tomografía Computarizada por Rayos X/métodosRESUMEN
PURPOSE: Current nonvascular osseous reconstructive options for reconstruction of the orbital floor after maxillectomy include options such as scapular tip and iliac crest bone grafts. The aim of this study was to determine whether these donor sites were morphologically comparable with the orbital floor. MATERIALS AND METHODS: A retrospective cross-sectional study design was selected. By use of a pre-existing melanoma database (January 1, 2005, through September 20, 2015), computed tomography scans of the head, neck, thorax, and pelvis were obtained from patients without evidence of bony metastases. With the use of 3-dimensional software (Mimics; Materialise, Leuven, Belgium), grafts from the scapulae and iliac crests, the predictor variables, were digitally harvested, co-registered with the orbital floors bilaterally, and analyzed. The primary outcome was conformance. Data were analyzed using descriptive statistics and tests of statistical significance. The significance level was set at P<.05. RESULTS: The study sample included 10 patients (6 men and 4 women; mean age, 55 ± 18 years). Close conformance was observed when we analyzed the morphology of the orbital floor to the scapular (2.23 ± 0.31 mm) and iliac crest (2.13 ± 0.30 mm) bone grafts, with no significant difference between sites. Conformance mapping showed maximum conformance centrally (scapula, 0.001 ± 0.001 mm; iliac crest, 0.001 ± 0.001 mm), with decreased morphologic similarity peripherally (scapula, 6.09 ± 0.94 mm; iliac crest, 5.74 ± 0.88 mm). There was no significant difference in conformance between sides of graft harvest. CONCLUSIONS: When considering nonvascularized bone grafts for reconstruction of the orbital floor, both the scapula and iliac crest offer nearly complete conformance to the orbital floor structure and represent reasonable reconstructive options.
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Trasplante Óseo/métodos , Ilion/trasplante , Neoplasias Maxilares/cirugía , Melanoma/cirugía , Órbita/diagnóstico por imagen , Órbita/cirugía , Escápula/trasplante , Estudios Transversales , Femenino , Humanos , Masculino , Neoplasias Maxilares/diagnóstico por imagen , Melanoma/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: To develop and validate a smartphone based Virtual Reality Epley Maneuver System (VREMS) for home use. METHODS: A smartphone application was designed to produce stereoscopic views of a Virtual Reality (VR) environment, which when viewed after placing a smartphone in a virtual reality headset, allowed the user to be guided step-by-step through the Epley maneuver in a VR environment. Twenty healthy participants were recruited and randomized to undergo either assisted Epleys or self-administered Epleys following reading instructions from an Instructional Handout (IH). All participants were filmed and two expert Otologists reviewed the videos, assigning each participant a score (out of 10) for performance on each step. Participants rated their perceived workload by completing a validated task-load questionnaire (NASA Task Load Index) and averages for both groups were calculated. RESULTS: Twenty participants were evaluated with average age 26.4±7.12years old in the VREMS group and 26.1±7.72 in the IH group. The VR assisted group achieved an average score of 7.78±0.99 compared to 6.65±1.72 in the IH group. This result was statistically significant with p=0.0001 and side dominance did not appear to play a factor. Analyzing each step of the Epley maneuver demonstrated that assisted Epleys were done more accurately with statically significant results in steps 2-4. Results of the NASA-TLX scores were variable with no significant findings. CONCLUSION: We have developed and demonstrated face validity for VREMS through our randomized controlled trial. The VREMS platform is promising technology, which may improve the accuracy and effectiveness of home Epley treatments. LEVEL OF EVIDENCE: N/A.
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Reconocimiento Facial/fisiología , Posicionamiento del Paciente/métodos , Modalidades de Fisioterapia/instrumentación , Postura/fisiología , Teléfono Inteligente , Realidad Virtual , Adulto , Vértigo Posicional Paroxístico Benigno/fisiopatología , Vértigo Posicional Paroxístico Benigno/terapia , Diseño de Equipo , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE(S): The purpose of this study was to compare computer-assisted mandibular plating to conventional plating using quantitative metrics. METHODS: Patients scheduled to undergo mandibular reconstruction were randomized to three-dimensional modelling for preoperative plate bending or intraoperative freehand bending. Preoperative and postoperative head and neck computed tomography scans were obtained to generate computer models of the reconstruction. The overall plate surface contact area, mean plate-to-bone distance, degree of conformance, and position of the condylar head within the glenoid fossa between pre- and post-operative scans were calculated. RESULTS: Twenty patients were included with a mean age of 57.8 years (standard deviation [SD] = 13.6). The mean follow-up time was 9.8 months (range = 1.6-22.3). Reconstruction was performed with fibular (25%) or scapular free flaps (75%). The percentage of surface contact between the reconstructive plate and mandible was improved with three-dimensional models compared to freehand bending (93.9 ± 7.7% vs. 78.0 ± 19.9%, p = 0.04). There was improved overall plate-to-bone distance (3D model: 0.7 ± 0.31 mm vs. conventional: 1.3 ± 0.8 mm, p = 0.06). Total intraoperative time was non-significantly decreased with the use of a model (3D model: 726.5 ± 89.1 min vs. conventional: 757.3 ± 84.1 min, p = 0.44). There were no differences in condylar head position or postoperative complications. CONCLUSION: Computer-assisted mandibular plating can be used to improve the accuracy of plate contouring. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:2182-2186, 2024.
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Colgajos Tisulares Libres , Reconstrucción Mandibular , Cirugía Asistida por Computador , Humanos , Persona de Mediana Edad , Proyectos Piloto , Reconstrucción Mandibular/métodos , Colgajos Tisulares Libres/cirugía , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Tomografía Computarizada por Rayos X , Peroné/cirugía , Cirugía Asistida por Computador/métodosRESUMEN
Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer-containing building blocks (â¼94,000 photosensitizers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumor ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma (OCSCC): biologically relevant subcutaneous Cal-33 (cell line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumors selectively uptake PS (10 mg/kg, i.v.) with 6-to 40-fold greater concentration versus muscle 24 hours post-injection. Single PS nanoparticle-mediated PDT (PS-PDT) treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumors yielded significant apoptosis in 65.7% of tumor cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumor models. Complete tumor response was achieved in 65% of Cal-33 and 91% of MOC22 tumor mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumors, respectively. In buccal VX-2 rabbit tumors, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumors. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes. SIGNIFICANCE: PS-PDT is a safe and repeatable treatment modality for OCSCC ablation. PS demonstrated tumor selective uptake and PS-PDT treatments achieved reproducible efficacy and effectiveness in multiple tumor models superior to other clinically tested photosensitizer drugs. Cosmetic and functional outcomes were excellent, and no clinically significant treatment-associated toxicities were detected. These results are enabling of window of opportunity trials for fluorescence-guided PS-PDT in patients with early-stage OCSCC scheduled for surgery.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Nanopartículas , Compuestos Organotiofosforados , Fotoquimioterapia , Humanos , Animales , Conejos , Ratones , Fármacos Fotosensibilizantes/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/inducido químicamente , Fotoquimioterapia/métodos , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/inducido químicamente , Nanopartículas/uso terapéuticoRESUMEN
Background: Reconstruction of mandibular bone defects is a surgical challenge, and microvascular reconstruction is the current gold standard. The field of tissue bioengineering has been providing an increasing number of alternative strategies for bone reconstruction. Methods: In this preclinical study, the performance of two bioengineered scaffolds, a hydrogel made of polyethylene glycol-chitosan (HyCh) and a hybrid core-shell combination of poly (L-lactic acid)/poly ( ε -caprolactone) and HyCh (PLA-PCL-HyCh), seeded with different concentrations of human mesenchymal stromal cells (hMSCs), has been explored in non-critical size mandibular defects in a rabbit model. The bone regenerative properties of the bioengineered scaffolds were analyzed by in vivo radiological examinations and ex vivo radiological, histomorphological, and immunohistochemical analyses. Results: The relative density increase (RDI) was significantly more pronounced in defects where a scaffold was placed, particularly if seeded with hMSCs. The immunohistochemical profile showed significantly higher expression of both VEGF-A and osteopontin in defects reconstructed with scaffolds. Native microarchitectural characteristics were not demonstrated in any experimental group. Conclusion: Herein, we demonstrate that bone regeneration can be boosted by scaffold- and seeded scaffold-reconstruction, achieving, respectively, 50% and 70% restoration of presurgical bone density in 120 days, compared to 40% restoration seen in spontaneous regeneration. Although optimization of the regenerative performance is needed, these results will help to establish a baseline reference for future experiments.
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Surgical navigation technology combines patient imaging studies with intraoperative real-time data to improve surgical precision and patient outcomes. The navigation workflow can also include preoperative planning, which can reliably simulate the intended resection and reconstruction. The advantage of this approach in skull-base surgery is that it guides access into a complex three-dimensional area and orients tumors intraoperatively with regard to critical structures, such as the orbit, carotid artery and brain. This enhances a surgeon's capabilities to preserve normal anatomy while resecting tumors with adequate margins. The aim of this narrative review is to outline the state of the art and the future directions of surgical navigation in the skull base, focusing on the advantages and pitfalls of this technique. We will also present our group experience in this field, within the frame of the current research trends.
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Exact placement of bone conduction implants requires avoidance of critical structures. Existing guidance technologies for intraoperative placement have lacked widespread adoption given accessibility challenges and significant cognitive loading. The purpose of this study is to examine the application of augmented reality (AR) guided surgery on accuracy, duration, and ease on bone conduction implantation. Five surgeons surgically implanted two different types of conduction implants on cadaveric specimens with and without AR projection. Pre- and postoperative computer tomography scans were superimposed to calculate centre-to-centre distances and angular accuracies. Wilcoxon signed-rank testing was used to compare centre-to-centre (C-C) and angular accuracies between the control and experimental arms. Additionally, projection accuracy was derived from the distance between the bony fiducials and the projected fiducials using image guidance coordinates. Both operative time (4.3 ± 1.2 min. vs. 6.6 ± 3.5 min., p = 0.030) and centre-to-centre distances surgery (1.9 ± 1.6 mm vs. 9.0 ± 5.3 mm, p < 0.001) were significantly less in augmented reality guided surgery. The difference in angular accuracy, however, was not significantly different. The overall average distance between the bony fiducial markings and the AR projected fiducials was 1.7 ± 0.6 mm. With direct intraoperative reference, AR-guided surgery enhances bone conduction implant placement while reduces operative time when compared to conventional surgical planning.
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Realidad Aumentada , Cirugía Asistida por Computador , Humanos , Cirugía Asistida por Computador/métodos , Conducción Ósea , Imagenología Tridimensional/métodos , Marcadores FiducialesRESUMEN
Background and purpose: Brain radiotherapy (cnsRT) requires reproducible positioning and immobilization, attained through redundant dedicated imaging studies and a bespoke moulding session to create a thermoplastic mask (T-mask). Innovative approaches may improve the value of care. We prospectively deployed and assessed the performance of a patient-specific 3D-printed mask (3Dp-mask), generated solely from MR imaging, to replicate a reproducible positioning and tolerable immobilization for patients undergoing cnsRT. Material and methods: Patients undergoing LINAC-based cnsRT (primary tumors or resected metastases) were enrolled into two arms: control (T-mask) and investigational (3Dp-mask). For the latter, an in-house designed 3Dp-mask was generated from MR images to recreate the head positioning during MR acquisition and allow coupling with the LINAC tabletop. Differences in inter-fraction motion were compared between both arms. Tolerability was assessed using patient-reported questionnaires at various time points. Results: Between January 2020 - July 2022, forty patients were enrolled (20 per arm). All participants completed the prescribed cnsRT and study evaluations. Average 3Dp-mask design and printing completion time was 36 h:50 min (range 12 h:56 min - 42 h:01 min). Inter-fraction motion analyses showed three-axis displacements comparable to the acceptable tolerance for the current standard-of-care. No differences in patient-reported tolerability were seen at baseline. During the last week of cnsRT, 3Dp-mask resulted in significantly lower facial and cervical discomfort and patients subjectively reported less pressure and confinement sensation when compared to the T-mask. No adverse events were observed. Conclusion: The proposed total inverse planning paradigm using a 3D-printed immobilization device is feasible and renders comparable inter-fraction performance while offering a better patient experience, potentially improving cnsRT workflows and its cost-effectiveness.
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BACKGROUND: Balloon dilation of the eustachian tube is a new therapeutic option for eustachian tube dysfunction. One of the limiting factors of wider adoption of this technique in many parts of the world is the high cost of the devices, in spite of regulatory approval of safety. OBJECTIVE: Evaluate the performance and usability of standard less-expensive endovascular balloons for eustachian tube dilation in comparison to an approved device in a preclinical study. STUDY DESIGN: Comparative cadaver feasibility study. SETTING: University tertiary care facility. METHODS: Ten eustachian tube dilations were performed with an approved eustachian tube dilation device. Ten other procedures were carried out with an endovascular balloon of similar dimensions. Cone beam computerized tomography was performed to evaluate the extent of dilation and possible damages. The lumen and mucosal lining were inspected endoscopically post-dilation. Volume measurements were compared before and after the procedure in both groups using contrast enhancement. RESULTS: All 20 eustachian tube dilations were carried out successfully. No tissue damages could be identified on cone-beam computerized tomography or via endoscopic examination. There was a statistically significant difference of eustachian tube volumes between pre- and post-dilations, with no statistically significant difference between the devices. CONCLUSION: Eustachian tube dilation with a less costly endovascular balloon achieved similar results to an approved eustachian tube dilation device. No damages or any other safety concerns were identified in a cadaver study.
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Enfermedades del Oído , Trompa Auditiva , Cadáver , Dilatación/métodos , Enfermedades del Oído/cirugía , Trompa Auditiva/cirugía , Estudios de Factibilidad , HumanosRESUMEN
OBJECTIVES/HYPOTHESIS: Despite considerable effort being dedicated to contouring reconstruction plates, there remains limited evidence demonstrating an association between contour and reconstructive outcomes. We sought to evaluate whether optimizing mandibular reconstruction plate contouring is associated with reduced postoperative hardware complications. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort study was performed with adult patients (age ≥18 years) who underwent mandibulectomy and osseous free flap reconstruction following oncologic ablation at the University Health Network in Toronto, Canada, between January 1, 2003 and December 31, 2014. Patients with computed tomography scans performed within 1 year of reconstruction were included. Computer-based three-dimensional models were generated and used to calculate the mean plate-to-bone gap (mm). The primary outcome was plate exposure. Secondary outcome included a composite of plate exposure or intraoral dehiscence. Logistic regression models were fitted for each outcome accounting for other patient and surgical characteristics associated with the primary outcome. RESULTS: Ninety-four patients met inclusion criteria, with a mean age of 60.4 (standard deviation [SD] 14.9). The mean follow-up time was 31.4 months (range 3-94). Reconstruction was performed with fibular (57%) and scapular free flaps (43%). In the multivariable model, small mean plate-to-bone gap (<1 mm) was independently associated with 86% reduced odds of plate exposure (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.02-0.55). Mean plate-to-bone gap less than 1 mm was also independently associated with reduced odds of developing a composite of plate exposure or intraoral dehiscence (OR, 0.29; 95%CI, 0.11-0.75). CONCLUSION: Optimizing plate contouring during mandibular reconstruction may decrease the development of postoperative hardware complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:61-66, 2022.
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Placas Óseas , Reconstrucción Mandibular/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Placas Óseas/efectos adversos , Femenino , Colgajos Tisulares Libres/cirugía , Humanos , Masculino , Osteotomía Mandibular/métodos , Reconstrucción Mandibular/efectos adversos , Reconstrucción Mandibular/instrumentación , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Current massive pulmonary embolism (PE) animal models use central venous access to deliver blood clots, which have features of random clot distribution and potentially fatal hemodynamic compromise. A clinically relevant preclinical model for generating pulmonary emboli in a more controlled fashion would be of value for a variety of research studies, including initial evaluation of novel therapeutic approaches. Endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) is a newly established approach for peri-tracheal/bronchial targets. The purpose of the present work was to establish a minimally invasive PE model in swine via a transbronchial approach. Methods: In anesthetized Yorkshire pigs, a 21-G EBUS-guided transbronchial needle aspiration (EBUS-TBNA) needle was introduced into the pulmonary artery under EBUS guidance. Autologous blood clots were administered into the right and left lower pulmonary arteries sequentially (PE1 and PE2, respectively). Hemodynamic and biochemical responses were evaluated. Results: Ten pigs were evaluated; all 20 blood clots (6.3±1.9 mL) were successfully injected. After injection, mean pulmonary artery pressure (mPAP; mmHg) increased (baseline: 16.6±5.6 vs. PE1: 24.5±7.6, P<0.0001 vs. PE2: 26.9±6.7, P<0.0001), and a positive correlation was observed between clot volume and change in mPAP (PE1: r=0.69, P=0.025; PE1 + PE2: r=0.60, P=0.063). Mean arterial pressure (MAP; mmHg) (baseline: 57.5±5.1 vs. PE1: 59.0±9.1, P=0.918 vs. PE2: 60.9±9.6, P=0.664) remained stable. No complications were observed. Conclusions: EBUS allows minimally invasive, precise, and reliable generation of pulmonary emboli in pigs. This model may serve as an important tool for new PE-related diagnostic and therapeutic research.
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Computer-assisted surgery (CAS) can improve surgical precision in orthopaedic oncology. Accurate alignment of the patient's imaging coordinates with the anatomy, known as registration, is one of the most challenging aspects of CAS and can be associated with substantial error. Using intraoperative, on-the-table, cone-beam computed tomography (CBCT), we performed a pilot clinical study to validate a method for automatic intraoperative registration. Methods: Patients who were ≥18 years of age, had benign bone tumors, and underwent resection were prospectively enrolled. In addition to inserting a navigation tracking tool into the exposed bone adjacent to the surgical field, 2 custom plastic ULTEM tracking tools (UTTs) were attached to each patient's skin adjacent to the tumor using an adhesive. These were automatically localized within the 3-dimensional CBCT volume to be used as image landmarks for registration, and the corresponding tracker landmarks were captured using an infrared camera. The main outcomes were the fiducial registration error (FRE) and the target registration error (TRE). The navigation time was recorded. Results: Thirteen patients with benign tumors in the femur (n = 10), tibia (n = 2), and humerus (n = 1) underwent navigation-assisted resections. The mean values were 0.67 ± 0.15 mm (range, 0.47 to 0.97 mm) for FRE and 0.83 ± 0.51 mm (range, 0.42 to 2.28 mm) for TRE. Registration was successful in all cases. The mean time for CBCT imaging and tracker registration was 7.5 minutes. Conclusions: We present a novel automatic registration method for CAS exploiting intraoperative CBCT capabilities, which provided improved accuracy and reduced operative times compared with more traditional methods. Clinical Relevance: This proof-of-principle study validated a novel process for automatic registration to improve the accuracy of resecting bone tumors using a surgical navigation system.
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Background: Conventional flexible bronchoscopy has not achieved the high diagnostic yield for intrapulmonary lesions as seen with image-guided transthoracic biopsy. A thin convex probe endobronchial ultrasound bronchoscope (TCP-EBUS) with a 5.9-mm tip was designed to improve peripheral access over conventional EBUS bronchoscopes to facilitate real-time sampling of intrapulmonary lesions under ultrasound guidance. Methods: TCP-EBUS was inserted into the distal airways of ex-vivo human lungs to assess bronchial accessibility relative to clinically available bronchoscopes. The short- (≤1 h) and medium-term (≤10 d) safety of TCP-EBUS insertion and EBUS-guided transbronchial needle aspiration (TBNA) using a 25-gauge needle were evaluated physiologically and radiologically in live pigs. TCP-EBUS-guided TBNA feasibility was assessed in-vivo with pig intrapulmonary pseudo-tumors and ex-vivo with resected human lung cancer specimens. Results: For bronchial accessibility, TCP-EBUS demonstrated greater reach than the 6.6-mm convex probe endobronchial ultrasound (CP-EBUS) in all bronchi, as well as surpassed a 5.5-mm conventional bronchoscope in 63% (131/209) and a 4.8-mm conventional bronchoscope in 27% (57/209) of assessed bronchi. The median bronchial generation and the mean diameter of bronchi TCP-EBUS reached was 4 (range, 3-7) and 3.3±0.7 mm, respectively. No major complications related to TCP-EBUS-guided TBNA in distal airways were observed in the live pigs. Scattered mucosal erythema of the bronchial walls was observed immediately after TCP-EBUS insertion; this self-resolved by day 10. TCP-EBUS could successfully reach and visualize intrapulmonary targets via ultrasound, with no difficulty in needle deployment or sampling. Conclusions: TCP-EBUS has the potential to facilitate safe real-time transbronchial sampling of intrapulmonary lesions in the central and middle lung fields.