124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of ¹⁸F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized C_H2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaC_H2), radiolabeled with iodine-124 (¹²⁴I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging.</p> <p>Methods</p> <p>HuCC49deltaC_H2 was radiolabeled with ¹²⁴I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of ¹²⁴I-HuCC49deltaC_H2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of ¹⁸F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection.</p> <p>Results</p> <p>At approximately 1 hour after i.v. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, ¹²⁴I-HuCC49deltaC_H2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, ¹⁸F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder.</p> <p>Conclusions</p> <p>On microPET imaging, ¹²⁴I-HuCC49deltaC_H2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while ¹⁸F-FDG failed to demonstrate this. The antigen-directed and cancer-specific ¹²⁴I-radiolabled anti-TAG-72 monoclonal antibody conjugate, ¹²⁴I-HuCC49deltaC_H2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.</p

Optimization of computer-assisted intraoperative guidance for complex oncological procedures

Mención Internacional en el título de doctorThe role of technology inside the operating room is constantly increasing, allowing surgical procedures previously considered impossible or too risky due to their complexity or limited access. These reliable tools have improved surgical efficiency and safety. Cancer treatment is one of the surgical specialties that has benefited most from these techniques due to its high incidence and the accuracy required for tumor resections with conservative approaches and clear margins. However, in many cases, introducing these technologies into surgical scenarios is expensive and entails complex setups that are obtrusive, invasive, and increase the operative time. In this thesis, we proposed convenient, accessible, reliable, and non-invasive solutions for two highly complex regions for tumor resection surgeries: pelvis and head and neck. We explored how the introduction of 3D printing, surgical navigation, and augmented reality in these scenarios provided high intraoperative precision. First, we presented a less invasive setup for osteotomy guidance in pelvic tumor resections based on small patient-specific instruments (PSIs) fabricated with a desktop 3D printer at a low cost. We evaluated their accuracy in a cadaveric study, following a realistic workflow, and obtained similar results to previous studies with more invasive setups. We also identified the ilium as the region more prone to errors. Then, we proposed surgical navigation using these small PSIs for image-to-patient registration. Artificial landmarks included in the PSIs substitute the anatomical landmarks and the bone surface commonly used for this step, which require additional bone exposure and is, therefore, more invasive. We also presented an alternative and more convenient installation of the dynamic reference frame used to track the patient movements in surgical navigation. The reference frame is inserted in a socket included in the PSIs and can be attached and detached without losing precision and simplifying the installation. We validated the setup in a cadaveric study, evaluating the accuracy and finding the optimal PSI configuration in the three most common scenarios for pelvic tumor resection. The results demonstrated high accuracy, where the main source of error was again incorrect placements of PSIs in regular and homogeneous regions such as the ilium. The main limitation of PSIs is the guidance error resulting from incorrect placements. To overcome this issue, we proposed augmented reality as a tool to guide PSI installation in the patient’s bone. We developed an application for smartphones and HoloLens 2 that displays the correct position intraoperatively. We measured the placement errors in a conventional and a realistic phantom, including a silicone layer to simulate tissue. The results demonstrated a significant reduction of errors with augmented reality compared to freehand placement, ensuring an installation of the PSI close to the target area. Finally, we proposed three setups for surgical navigation in palate tumor resections, using optical trackers and augmented reality. The tracking tools for the patient and surgical instruments were fabricated with low-cost desktop 3D printers and designed to provide less invasive setups compared to previous solutions. All setups presented similar results with high accuracy when tested in a 3D-printed patient-specific phantom. They were then validated in the real surgical case, and one of the solutions was applied for intraoperative guidance. Postoperative results demonstrated high navigation accuracy, obtaining optimal surgical outcomes. The proposed solution enabled a conservative surgical approach with a less invasive navigation setup. To conclude, in this thesis we have proposed new setups for intraoperative navigation in two complex surgical scenarios for tumor resection. We analyzed their navigation precision, defining the optimal configurations to ensure accuracy. With this, we have demonstrated that computer-assisted surgery techniques can be integrated into the surgical workflow with accessible and non-invasive setups. These results are a step further towards optimizing the procedures and continue improving surgical outcomes in complex surgical scenarios.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidente: Raúl San José Estépar.- Secretario: Alba González Álvarez.- Vocal: Simon Droui

Polyurethane mesh and breast implant in a rat model

Le protesi al seno sono dispositivi medici utilizzati per scopi estetici e ricostruttivi al finedi migliorare le dimensioni e la forma del seno. La tasca sotto muscolare rappresenta lasede opportuna per il posizionamento delle protesi nel polo superiore. Tuttavia, in alcunicasi, il polo laterale e inferiore risultano coperti solo da uno strato sottile di pelle,predisponendo alla ptosi, al cedimento e all'estrazione dell'impianto. In molti casi,migliori risultati estetici e clinici possono essere ottenuti utilizzando una maglia per ilsupporto dell'impianto. Che si tratti di maglie biologiche o sintetiche, ci sono anche alcunipotenziali svantaggi nell'utilizzarle nella chirurgia basata sugli impianti mammarie,principalmente il rischio di infezione o rigetto. Il degrado della maglia può essereproblematico poiché l'assorbimento rapido può causare il cedimento dell'impianto o ladurabilità a lungo termine può produrre una continua reazione del corpo estraneo.Ipotesi: Lo sviluppo di una maglia fibrosa in PCUU + Tecoflex (PCUU-T) potrebbestimolare la crescita del tessuto con ridotta formazione di cicatrici e fornire supportomeccanico nei procedimenti di impianto mammarie rispetto ad altre maglie sintetiche.Obiettivo: Valutare l'uso della maglia non tessuta in PCUU-T come impalcatura inassociazione con un impianto mammario ed il suo comportamento in uno studiopreclinico su piccoli animali in confronto con la maglia commerciale Ultrapro.Metodo e Materiale: 1) Cinque maglie sintetiche sono state valutate attraverso test dispessore, densità, meccanici e di porosità. 2) Diverse concentrazioni di PCUU+T sonostate preparate e sottoposte a vari test (spessore, densità, degradazione, porosità e testmeccanici). 3) Uno studio in vivo è stato condotto con n=18 ratti Wistar femmine adulte(70 giorni di età). Gli esperimenti sono stati divisi in tre gruppi (6 ratti ciascuno),ricevendo maglia PCUU+T sul lato sinistro e maglia Ultrapro sul lato destro nei taschinidorsali sotto muscolari: Il primo gruppo Liscio (S) ha ricevuto mini-impianti mammarielisci per lato; il secondo gruppo Texture (T) ha ricevuto impianti testurizzati per lato, e ilterzo gruppo Maglia (M) è stato un gruppo di controllo che ha ricevuto solo la magliasenza impianti. Il peso dei ratti è stato misurato e il sangue è stato prelevato dalla codaprima e dopo l'intervento chirurgico per valutare la tossicità. Le complicanzepostoperatorie sono state analizzate con esame clinico e mediante ecografia. Dopol'eutanasia al giorno 63, il blocco è stato rimosso per valutazione istologica ebatteriologico.Risultati: La maglia Ultrapro ha rappresentato le migliori caratterizzazioni dellemaglie. La miscela 50:50 PCUU+T (spessore 374 μm, peso 46,33 mg, rapportoanisotropo 2,14, porosità 4,71). Il peso dei ratti è aumentato del 21% dal preoperatorio ai63 giorni (P&lt;0,05). L'89% dei ratti non ha avuto complicazioni. Nessuna presenza diseroma è stata identificata clinicamente e mediante ecografia. La batteriologia dopol'eutanasia è stata negativa all'88%, il 6% ha presentato Staphylococcus epidermidi e il6% Corynebacterium. Non sono state trovate cellule giganti sul lato PCUU-T in tutti igruppi; erano presenti solo nella maglia Ultrapro e avevano una significativaassociazione con gli impianti mammarie lisci. Inoltre, la maglia PCUU-T ha mostratosignificativamente meno plasmaciti e linfociti rispetto a Ultrapro. Una lieve fibrosi è5stata riconosciuta sulla periferia di Ultrapro. Gli eosinofili erano più elevati sulla pelledi controllo, il gruppo di impianti testurizzati sul lato PCUU-T ha mostrato più eosinofilirispetto a Ultrapro. I mastociti erano significativamente inferiori sul lato PCUU-Trispetto a Ultrapro. Ultrapro aveva una maggiore quantità di cellule infiammatorie. Ilgruppo M ha mostrato significativamente più numeri di vasi rispetto alla pelle dicontrollo. Congestione vascolare e depositi di emosiderina sono stati osservati nellamaglia Ultrapro. Il componente vascolare sul PCUU-T aveva caratteristiche moltosimili al gruppo di controllo M. Il risultato ha identificato una buona integrazione nellamaglia PCUU-T. La concentrazione di collagene su PCUU-T ha mostrato una formazionedi collagene inferiore rispetto a Ultrapro indipendentemente dalla superficiedell'impianto. I parametri ematologici erano simili nelle misurazioni pre e postoperatorie.Conclusioni: Questa ricerca ha sviluppato una nuova maglia non tessuta nano fibrosaparzialmente biodegradabile di PCUU-T. Questa maglia progettata è stata utilizzata comeimpalcatura in associazione con un impianto mammarie in un modello di ratto econfrontata con la maglia parzialmente assorbibile Ultrapro nel dorso di un modello diratto. I risultati della nuova maglia sono stati associati alla più bassa risposta del corpoestraneo, senza formazione di cellule giganti e con un buon grado di deposizione di nuovocollagene e rimodellamento della matrice. Adatta per l'integrazione del tessuto nativo, laguarigione e il rimodellamento del tessuto, con un buon rapporto di anisotropia per forniresupporto futuro per la ricostruzione basata sull'impianto mammarie.Parole chiave: Poli (carbonato-urea-uretano), Tecoflex, Ultrapro, maglia, biomateriale,elettrofilatura, ricostruzione basata sull'impianto mammarie.Breast implants are used for aesthetic and reconstructive purposes to enhance the size andshape of the breast. The submuscular pocket provides upper pole coverage. However, thelateral and inferior pole could be covered only by the thin skin, predisposing to ptosis,bottoming out, and implant extrusion. Better results can be achieved by using mesh toimplant support. Whether it is biological or synthetic meshes, there are also somepotential drawbacks, such as infection or rejection. The mesh degradation can beproblematic since rapid absorption can cause implant bottoming out, or long-lastingdurability can produce a continued foreign body reaction.Hypothesis: PCUU + Tecoflex (PCUU-T) nanofiber mesh could stimulate tissueingrowth with reduced scar formation and provide mechanical support in breast implantprocedures compared to other synthetic meshes.Objective: To evaluate the use of biodegradable Poly (carbonate- urethane) urea (PCUU)plus non-degradable Tecoflex (PCUU-T) nonwoven mesh as a scaffold in associationwith a breast implant and its behavior in a small animal preclinical study in comparisonwith commercial mesh Ultrapro.Method and Material: 1) Five synthetic meshes were evaluated through the thickness,density, mechanical, and porosity tests. 2) Different blends of PCUU+T concentrationwere prepared and underwent several tests (thickness, density, degradation, porosity, andmechanical tests). 3) An in vivo study was conducted with n=18 adult female Wistar rats(70 days old). Experiments were divided into three groups (6 rats each), receivingPCUU+T mesh on the left side and Ultrapro mesh on the right side on the subdermaldorsal pockets: Smooth group (S) received smooth mini-breast implants per side; Texturegroup (T) received textured implants per side, and Mesh group (M) was a control groupthat received mesh without implants. The rats' weight was measured, and blood wascollected before and after surgery to assess toxicity. Postoperative complications wereanalyzed with clinical exam and by ultrasound. After euthanasia on day 63, the blockwere removed for histological and bacteriological evaluation.Results: Ultrapro mesh represented the best characterization mesh. The 50:50PCUU+T blend was selected (thickness 374 m, weight 46.33mg, anisotropic ratio 2.14,porosity 4.71). Rats’ weights increased by 21% from the preoperative to 63 days(P&lt;0,05). 89% of the rats have no complications. No presence of seroma was identified.Bacteriology was 88% negative, 6% presented Staphylococcus epidermidis, and 6%Corynebacterium. No giant cells were found on the PCUU-T in all groups; they were onlypresent in the Ultrapro most with smooth implants. PCUU-T mesh showed significantlyfewer plasmacytes and lymphocytes than Ultrapro. Eosinophils were higher on controlskin. Mast cells were significantly lower on the PCUU-T. Ultrapro had a greater amountof inflammatory cells. Group M showed significantly more numbers of vessels than thecontrol skin. Vascular congestion and hemosiderin deposits were observed withUltrapro. The vascular component on the PCUU-T was similar to the control group M.The collagen concentration on PCUU-T showed less collagen formation than Ultrapro,whatever the implant surface. Hematological parameters were similar in the pre andpostoperative measures.Conclusion: This research developed a novel nanofiber partially biodegradableelectrospun PCUU-T nonwoven mesh. This designed mesh was used as a scaffold inassociation with a breast implant in a rat model and compared with partially absorbableUltrapro mesh in the respective dorsum of a rat model.The outcomes of the novel mesh were associated with the lowest foreign body response,without giant cell formation, a good degree of new collagen deposition, and matrix4remodeling. It is suitable for native tissue integration, healing, and remodeling tissue,with a good anisotropy ratio to provide future support for breast implant-basereconstruction.Keywords: Poly(carbonate- -urethane) urea, Tecoflex, Ultrapro, mesh, biomaterial,electrospinning, breast implant-base reconstruction

Innovations in the Integrated Management of Breast Cancer

Breast cancer is acknowledged as an international priority in healthcare. It is currently the most common cancer in women worldwide, with demographic trends indicating a continuous increase in incidence. Over the years, increasing efforts and resources have been devoted to the search for a systematic and optimized strategy in breast cancer diagnosis and treatment. Today, the Breast Unit model is considered the gold standard in order to ensure optimal patient-centered and research-based clinical services through multidisciplinary and integrated management.Surgical treatment has gradually evolved toward less aggressive approaches with the adoption of new therapeutic strategies. The evolution of evidence-based guidelines in such leading disciplines as radiation and medical oncology has led to a steady improvement in survival rates. This Special Issue will highlight innovations in the integrated management of breast cancer, their potential advantages, and the many open issues that still need to be properly defined and addressed

A structured-light surface scanning system to evaluate breast morphology in standing and supine positions

Objective and accurate surface measurements of the human breast are important for surgical planning and outcome assessment. Breast shapes are affected by gravitational loads and deformities, and the measurements obtained in the standing position may not correlate well with measurements in supine position, which is more representative of breast surgery. To evaluate the effect of changes in body posture on breast morphology, a dual color 3D surface imaging system capable of scanning patients in both the supine and standing positions was developed. System performance was established by assessing the surface coverage and accuracy between a CAD breast model and 3D surface scans of a 3D print of the CAD model. The modular nature of the system offers the potential to add additional surface scanners with unique colors to increase coverage without sacrificing speed. The human pilot study shows that the system can quantitatively evaluate the effect of subject postures in individuals with smaller breasts, and thereby has the potential to be used to investigate changes in breast morphologies

Turning data into decisions : clinical decision support in orthopaedic oncology

Background: The treatment of patients with skeletal metastases is predicated on each patient’s estimated survival. In order to maximize function and quality of life, orthopaedic surgeons must carefully avoid over- or undertreatment of the disease. Unfortunately, physician estimates are notoriously inaccurate and there are no validated means by which to estimate patient survival in patients with long-bone skeletal metastases. The purpose of this thesis is to apply machine learning (ML) approaches to (1) develop a clinical decision support (CDS) tool capable of estimating survival in patients with operable skeletal metastases, and (2) establish guidelines so that this approach may be used in other relevant topics within the field of orthopaedics. Methods: We first defined the scope of the problem using data from the Karolinska Skeletal Metastasis Registry. We then developed objective criteria by which to estimate patient survival using data gleaned from the Memorial Sloan-Kettering Skeletal Metastasis Database (n=189). We employed ML techniques to find patterns within the data associated with short- and long-term survival. We chose three and 12 months because they are widely accepted to guide orthopaedic surgical decisionmaking. We developed an Artificial Neural Network (ANN), a Bayesian Belief Network (BBN), and a traditional Logistic Regression (LR) model. Each resulting model was internally validated and compared using Receiver Operator Characteristic (ROC) analysis. In addition, we performed decision analysis to determine which model, if any, was suited for clinical use. Next, we externally validated the models using Scandinavian Registry data (n=815), and again using data collected by the Societ. Italiana di Ortopedia e Traumatologia (SIOT) (n=287). We then created a web-based CDS tool as well as the infrastructure to collect prospective data on a global scale, so the models could be improved over time. Finally, we used BBN modeling to describe the hierarchical relationships between features associated with the treatment of highgrade soft tissue sarcomas (STS), and codify this complex information into a graphical representation to promote a more thorough understanding of the disease process. Results: We found that implant failures in patients with skeletal metastases remain relatively common—even in the revision setting—as patients outlive their implants. On the other hand, perioperative deaths are relatively common, indicating that an estimation of life expectancy should be part of the surgical decision making process. Using ML approaches, we found several criteria that can be used to estimate longevity in this patient population. When compared to other techniques, the ANN model was most accurate, and also resulted in highest net benefit on decision analysis, compared to the BBN and LR models. However, the BBN is the best suited to accommodate missing data, which is common in the clinical setting. The three- and 12-month BBN models were successfully externally validated using the SSMR database (Area under the ROC curve (AUC) of 0.79 and 0.76, respectively), and again using SIOT data (AUC 0.80 and 0.77). In the setting of high-grade, completely excised STS, BBN Modeling identified the first-degree associates of disease-specific survival to be the size of the primary tumor, and the presence and timing of local and distant recurrence. Conclusions: We successfully developed and validated a CDS tool designed to estimate survival in patients with operable skeletal metastases. In addition, we made this tool available to orthopaedic surgeons, worldwide, at www.pathfx.org. We also created an international skeletal metastasis registry to continue to collect data on patients with skeletal metastases. Within this framework, prognostic models have the capacity to improve over time, as treatment philosophies evolve and more effective systemic therapies become available. These techniques may now be applied to other disciplines, in an effort to turn quality data into decision support tools

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p &lt; 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p &lt; 0.001). Males were significantly more likely to be admitted than females (p &lt; 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

'Clinical Triad' findings in Klippel-feil patients

E-Poster - Congenital Deformity: no. 530It has been propagated that Klippel-Feil Syndrome (KFS) is associated with the clinical triad findings (CTF) of short neck, low posterior hairline, and limited range of motion. This study noted that CTFs are not consistently noted in KFS patients. KFS patients with extensive congenitally fused cervical segments were more likely to exhibit one of the components of CTF.postprin

Selection of fusion levels in adolescent idiopathic scoliosis (AIS) using the fulcrum bending radiograph prediction: verification based on pedicle screw strategy

E-Poster - Adolescent Idiopathic Scoliosis: no. 297Utilizing the fulcrum bending radiographic technique to assess curve flexibility to aid in the selection of fusion levels, a prospective radiographic study was performed to assess the safety and effectiveness of pedicle screw fixation with alternate level screw strategy (ALSS) for thoracic AIS. This study suggests that ALSS obtains greater deformity correction than hook and hybrid systems, and improves balance without compromising fusion levels.postprin

Book of Abstracts 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization

In this edition, the two events will run together as a single conference, highlighting the strong connection with the Taylor & Francis journals: Computer Methods in Biomechanics and Biomedical Engineering (John Middleton and Christopher Jacobs, Eds.) and Computer Methods in Biomechanics and Biomedical Engineering: Imaging and Visualization (JoãoManuel R.S. Tavares, Ed.). The conference has become a major international meeting on computational biomechanics, imaging andvisualization. In this edition, the main program includes 212 presentations. In addition, sixteen renowned researchers will give plenary keynotes, addressing current challenges in computational biomechanics and biomedical imaging. In Lisbon, for the first time, a session dedicated to award the winner of the Best Paper in CMBBE Journal will take place. We believe that CMBBE2018 will have a strong impact on the development of computational biomechanics and biomedical imaging and visualization, identifying emerging areas of research and promoting the collaboration and networking between participants. This impact is evidenced through the well-known research groups, commercial companies and scientific organizations, who continue to support and sponsor the CMBBE meeting series. In fact, the conference is enriched with five workshops on specific scientific topics and commercial software.info:eu-repo/semantics/draf