NaRALap: augmented reality system for navigation in laparoscopic surgery

The final publication is available at Springer via http://dx.doi.org/10.1007/s11548-011-0579-z.The AR system has a good resolution and currently is used for the placement of the trocars. Possible improvements will be performed to make the system independent of the camera position or to use natural marks. The biomechanical model and the AR algorithms will be combined with a tracker, for tracking the surgical instruments, in order to implement a valid system for liver biopsies. It will take into account the deformation due to the pneumoperitoneum and due to the breath of the patient. To develop the navigator that will guide the laparoscopic interventions, both AR system and biomechanical model will be combined with the laparoscopic camera in order to make an easier environment with only one vision in a 2D monitor.This work has been supported by the project MITYC (ref. TSI020100-2009-189). We would like to express our deep gratitude to the Hospital Clínica Benidorm for its participation in this project.López-Mir, F.; Martínez Martínez, F.; Fuertes Cebrián, JJ.; Lago, MA.; Rupérez Moreno, MJ.; Naranjo Ornedo, V.; Monserrat Aranda, C. (2011). NaRALap: augmented reality system for navigation in laparoscopic surgery. International Journal of Computer Assisted Radiology and Surgery. 6:98-99. https://doi.org/10.0.3.239/s11548-011-0579-zS9899

Patient-specific simulation environment for surgical planning and preoperative rehearsal

Surgical simulation is common practice in the fields of surgical education and training. Numerous surgical simulators are available from commercial and academic organisations for the generic modelling of surgical tasks. However, a simulation platform is still yet to be found that fulfils the key requirements expected for patient-specific surgical simulation of soft tissue, with an effective translation into clinical practice. Patient-specific modelling is possible, but to date has been time-consuming, and consequently costly, because data preparation can be technically demanding. This motivated the research developed herein, which addresses the main challenges of biomechanical modelling for patient-specific surgical simulation. A novel implementation of soft tissue deformation and estimation of the patient-specific intraoperative environment is achieved using a position-based dynamics approach. This modelling approach overcomes the limitations derived from traditional physically-based approaches, by providing a simulation for patient-specific models with visual and physical accuracy, stability and real-time interaction. As a geometrically- based method, a calibration of the simulation parameters is performed and the simulation framework is successfully validated through experimental studies. The capabilities of the simulation platform are demonstrated by the integration of different surgical planning applications that are found relevant in the context of kidney cancer surgery. The simulation of pneumoperitoneum facilitates trocar placement planning and intraoperative surgical navigation. The implementation of deformable ultrasound simulation can assist surgeons in improving their scanning technique and definition of an optimal procedural strategy. Furthermore, the simulation framework has the potential to support the development and assessment of hypotheses that cannot be tested in vivo. Specifically, the evaluation of feedback modalities, as a response to user-model interaction, demonstrates improved performance and justifies the need to integrate a feedback framework in the robot-assisted surgical setting.Open Acces

Design and Validation of an Augmented Reality System for Laparoscopic Surgery in a Real Environment

Purpose. This work presents the protocol carried out in the development and validation of an augmented reality system which was installed in an operating theatre to help surgeons with trocar placement during laparoscopic surgery. The purpose of this validation is to demonstrate the improvements that this system can provide to the field of medicine, particularly surgery. Method. Two experiments that were noninvasive for both the patient and the surgeon were designed. In one of these experiments the augmented reality system was used, the other one was the control experiment, and the system was not used. The type of operation selected for all cases was a cholecystectomy due to the low degree of complexity and complications before, during, and after the surgery. The technique used in the placement of trocars was the French technique, but the results can be extrapolated to any other technique and operation. Results and Conclusion. Four clinicians and ninety-six measurements obtained of twenty-four patients (randomly assigned in each experiment) were involved in these experiments.The final results show an improvement in accuracy and variability of 33% and 63%, respectively, in comparison to traditional methods, demonstrating that the use of an augmented reality system offers advantages for trocar placement in laparoscopic surgery.This work has been supported by Centro para el Desarrollo Tecnologico Industrial (CDTI) under the project Oncotic (IDI-20101153) and the Hospital Clinica Benidorm(HCB) and partially supported by the Ministry of Education and Science of Spain (TIN2010-20999-C04-01), the project Consolider-C (SEJ2006-14301/PSIC) and the "CIBER of Physiopathology of Obesity Nutrition, an initiative of ISCIII" Prometheus and Excellence Research Program (Generalitat Valenciana, Department of Education, 2008-157). The authors would like to express their gratitude to the Hospital Clinica Benidorm and to the Hospital Univeritari i Politecnic la Fe (especially the surgical team) for their participation and involvement in this work.López-Mir, F.; Naranjo Ornedo, V.; Fuertes Cebrián, JJ.; Alcañiz Raya, ML.; Bueno, J.; Pareja, E. (2013). Design and Validation of an Augmented Reality System for Laparoscopic Surgery in a Real Environment. BioMed Research International. 2013:1-12. https://doi.org/10.1155/2013/758491S1122013Rowe, C. K., Pierce, M. W., Tecci, K. C., Houck, C. S., Mandell, J., Retik, A. B., & Nguyen, H. T. (2012). A Comparative Direct Cost Analysis of Pediatric Urologic Robot-Assisted Laparoscopic Surgery Versus Open Surgery: Could Robot-Assisted Surgery Be Less Expensive? Journal of Endourology, 26(7), 871-877. doi:10.1089/end.2011.0584Azuma, R. T. (1997). A Survey of Augmented Reality. Presence: Teleoperators and Virtual Environments, 6(4), 355-385. doi:10.1162/pres.1997.6.4.355Shuhaiber, J. H. (2004). Augmented Reality in Surgery. Archives of Surgery, 139(2), 170. doi:10.1001/archsurg.139.2.170Kersten-Oertel, M., Jannin, P., & Collins, D. L. (2012). DVV: A Taxonomy for Mixed Reality Visualization in Image Guided Surgery. IEEE Transactions on Visualization and Computer Graphics, 18(2), 332-352. doi:10.1109/tvcg.2011.50Cannon, J. W., Stoll, J. A., Selha, S. D., Dupont, P. E., Howe, R. D., & Torchiana, D. F. (2003). Port placement planning in robot-assisted coronary artery bypass. IEEE Transactions on Robotics and Automation, 19(5), 912-917. doi:10.1109/tra.2003.817502Adhami, L., & Coste-Manirei, E. (2003). Optimal planning for minimally invasive surgical robots. IEEE Transactions on Robotics and Automation, 19(5), 854-863. doi:10.1109/tra.2003.817061Bichlmeier, C., Heining, S. M., Feuerstein, M., & Navab, N. (2009). The Virtual Mirror: A New Interaction Paradigm for Augmented Reality Environments. IEEE Transactions on Medical Imaging, 28(9), 1498-1510. doi:10.1109/tmi.2009.2018622Feuerstein, M., Mussack, T., Heining, S. M., & Navab, N. (2008). Intraoperative Laparoscope Augmentation for Port Placement and Resection Planning in Minimally Invasive Liver Resection. IEEE Transactions on Medical Imaging, 27(3), 355-369. doi:10.1109/tmi.2007.907327Abdominal and Laparoscopic Surgery. (2010). International Journal of Computer Assisted Radiology and Surgery, 5(S1), 122-130. doi:10.1007/s11548-010-0446-3Ferrari, V., Megali, G., Troia, E., Pietrabissa, A., & Mosca, F. (2009). A 3-D Mixed-Reality System for Stereoscopic Visualization of Medical Dataset. IEEE Transactions on Biomedical Engineering, 56(11), 2627-2633. doi:10.1109/tbme.2009.2028013McSherry, C. K. (1989). Cholecystectomy: The gold standard. The American Journal of Surgery, 158(3), 174-178. doi:10.1016/0002-9610(89)90246-8Kum, C.-K., Eypasch, E., Aljaziri, A., & Troidl, H. (1996). Randomized comparison of pulmonary function after the ‘French’ and ‘American’ techniques of laparoscopic cholecystectomy. British Journal of Surgery, 83(7), 938-941. doi:10.1002/bjs.1800830716Mischkowski, R. A., Zinser, M. J., Kübler, A. C., Krug, B., Seifert, U., & Zöller, J. E. (2006). Application of an augmented reality tool for maxillary positioning in orthognathic surgery – A feasibility study. Journal of Cranio-Maxillofacial Surgery, 34(8), 478-483. doi:10.1016/j.jcms.2006.07.862Kawamata, T., Iseki, H., Shibasaki, T., & Hori, T. (2002). Endoscopic Augmented Reality Navigation System for Endonasal Transsphenoidal Surgery to Treat Pituitary Tumors: Technical Note. Neurosurgery, 50(6), 1393-1397. doi:10.1097/00006123-200206000-00038Vogt, S., Khamene, A., & Sauer, F. (2006). Reality Augmentation for Medical Procedures: System Architecture, Single Camera Marker Tracking, and System Evaluation. International Journal of Computer Vision, 70(2), 179-190. doi:10.1007/s11263-006-7938-1Nicolau, S., Soler, L., Mutter, D., & Marescaux, J. (2011). Augmented reality in laparoscopic surgical oncology. Surgical Oncology, 20(3), 189-201. doi:10.1016/j.suronc.2011.07.002Zhang, Z. (2000). A flexible new technique for camera calibration. IEEE Transactions on Pattern Analysis and Machine Intelligence, 22(11), 1330-1334. doi:10.1109/34.888718Martín-Gutiérrez, J., Luís Saorín, J., Contero, M., Alcañiz, M., Pérez-López, D. C., & Ortega, M. (2010). Design and validation of an augmented book for spatial abilities development in engineering students. Computers & Graphics, 34(1), 77-91. doi:10.1016/j.cag.2009.11.003Marquardt, D. W. (1963). An Algorithm for Least-Squares Estimation of Nonlinear Parameters. Journal of the Society for Industrial and Applied Mathematics, 11(2), 431-441. doi:10.1137/011103

Advanced techniques in medical image segmentation of the liver

Tesis por compendio[EN] Image segmentation is, along with multimodal and monomodal registration, the operation with the greatest applicability in medical image processing. There are many operations and filters, as much as applications and cases, where the segmentation of an organic tissue is the first step. The case of liver segmentation in radiological images is, after the brain, that on which the highest number of scientific publications can be found. This is due, on the one hand, to the need to continue innovating in existing algorithms and, on the other hand, to the applicability in many situations related to diagnosis, treatment and monitoring of liver diseases but also for clinical planning. In the case of magnetic resonance imaging (MRI), only in recent years some solutions have achieved good results in terms of accuracy and robustness in the segmentation of the liver. However these algorithms are generally not user-friendly. In the case of computed tomography (CT) scans more methodologies and solutions have been developed but it is difficult to find a good trade-off between accuracy and practical clinical use. To improve the state-of-the-art in both cases (MRI and CT), a common methodology to design and develop two liver segmentation algorithms in those imaging modalities has been proposed in this thesis. The second step has been the validation of both algorithms. In the case of CT images, there exist public databases with images segmented manually by experts that the scientific community uses as a common link for the validation and comparison of their algorithms. The validation is done by obtaining certain coefficients of similarity between the manual and the automatic segmentation. This way of validating the accuracy of the algorithm has been followed in this thesis, except in the case of magnetic resonance imaging because, at present, there are no databases publicly available. In this case, there aren't public or accessible images. Accordingly, a private database has been created where several expert radiologists have manually segmented different studies of patients that have been used as a reference. This database is composed by 17 studies (with more than 1,500 images), so the validation of this method in MRI is one of the more extensive currently published. In the validation stage, an accuracy above 90% in the Jaccard and Dice coefficients has been achieved. The vast majority of the compared authors achieves similar values. However, in general, the algorithms proposed in this thesis are more user-friendly for clinical environments because the computational cost is lower, the clinical interaction is non-existent and it is not necessary an initiation in the case of the magnetic resonance algorithm and a small initiation (it is only necessary to introduce a manual seed) for the computed tomography algorithm. In this thesis, a third hypothesis that makes use of the results of liver segmentation in MRI combined to augmented reality algorithms has also been developed. Specifically, a real and innocuous study, non-invasive for clinician and patient has been designed and validated through it has been shown that the use of this technology creates benefits in terms of greater accuracy and less variability versus the non-use in a particular case of laparoscopic surgery.[ES] La segmentación de imágenes es, junto al registro multimodal y monomodal, la operación con mayor aplicabilidad en tratamiento digital de imagen médica. Son multitud las operaciones y filtros, así como las aplicaciones y casuística, que derivan de una segmentación de un tejido orgánico. El caso de segmentación del hígado en imágenes radiológicas es, después del cerebro, la que mayor número de publicaciones científicas podemos encontrar. Esto es debido por un lado a la necesidad de seguir innovando en los algoritmos ya existentes y por otro a la gran aplicabilidad que tiene en muchas situaciones relacionadas con el diagnóstico, tratamiento y seguimiento de patologías hepáticas pero también para la planificación clínica de las mismas. En el caso de imágenes de resonancia magnética, sólo en los últimos años han aparecido soluciones que consiguen buenos resultados en cuanto a precisión y robustez en la segmentación del hígado. Sin embargo dichos algoritmos, por lo general son poco utilizables en el ambiente clínico. En el caso de imágenes de tomografía computarizada encontramos mucha más variedad de metodologías y soluciones propuestas pero es difícil encontrar un equilibrio entre precisión y uso práctico clínico. Es por ello que para mejorar el estado del arte en ambos casos (imágenes de resonancia magnética y tomografía computarizada) en esta tesis se ha planteado una metodología común a la hora de diseñar y desarrollar sendos algoritmos de segmentación del hígado en las citadas modalidades de imágenes anatómicas. El segundo paso ha sido la validación de ambos algoritmos. En el caso de imágenes de tomografía computarizada existen bases de datos públicas con imágenes segmentadas manualmente por expertos y que la comunidad científica suele utilizar como nexo común a la hora de validar y posteriormente comparar sus algoritmos. La validación se hace mediante la obtención de determinados coeficientes de similitud entre la imagen segmentada manualmente por los expertos y las que nos proporciona el algoritmo. Esta forma de validar la precisión del algoritmo ha sido la seguida en esta tesis, con la salvedad que en el caso de imágenes de resonancia magnética no existen bases de datos de acceso público. Por ello, y para este caso, lo que se ha hecho es la creación previa de una base de datos propia donde diferentes expertos radiólogos han segmentado manualmente diferentes estudios de pacientes con el fin de que puedan servir como referencia y se pueda seguir la misma metodología que en el caso anterior. Dicha base de datos ha hecho posible que la validación se haga en 17 estudios (con más de 1.500 imágenes), lo que convierte la validación de este método de segmentación del hígado en imágenes de resonancia magnética en una de las más extensas publicadas hasta la fecha. La validación y posterior comparación han dejado patente una precisión superior al 90% reflejado en el coeficiente de Jaccard y Dice, muy en consonancia con valores publicados por la inmensa mayoría de autores que se han podido comparar. Sin embargo, y en general, los algoritmos planteados en esta tesis han obtenido unos criterios de uso mucho mayores, ya que en general presentan menores costes de computación, una interacción clínica casi nula y una iniciación nula en el caso del algoritmo de resonancia magnética y casi nula en el caso de algoritmos de tomografía computarizada. En esta tesis, también se ha abordado un tercer punto que hace uso de los resultados obtenidos en la segmentación del hígado en imágenes de resonancia magnética. Para ello, y haciendo uso de algoritmos de realidad aumentada, se ha diseñado y validado un estudio real inocuo y no invasivo para el clínico y para el paciente donde se ha demostrado que la utilización de esta tecnología reporta mayores beneficios en cuanto a mayor precisión y menor variabilidad frente a su no uso en un caso concreto de ciru[CA] La segmentació d'imatges és, al costat del registre multimodal i monomodal, l'operació amb major aplicabilitat en tractament digital d'imatge mèdica. Són multitud les operacions i filtres, així com les aplicacions i casuística, que comencen en la segmentació d'un teixit orgànic. El cas de segmentació del fetge en imatges radiològiques és, després del cervell, la que major nombre de publicacions científiques podem trobar. Això és degut per una banda a la necessitat de seguir innovant en els algoritmes ja existents i per un altre a la gran aplicabilitat que té en moltes situacions relacionades amb el diagnòstic, tractament i seguiment de patologies hepàtiques però també per a la planificació clínica de les mateixes. En el cas d'imatges de ressonància magnètica, només en els últims anys han aparegut solucions que aconsegueixen bons resultats quant a precisió i robustesa en la segmentació del fetge. No obstant això aquests algoritmes, en general són poc utilitzables en l'ambient clínic. En el cas d'imatges de tomografia computeritzada trobem molta més varietat de metodologies i solucions proposades però és difícil trobar un equilibri entre precisió i ús pràctic clínic. És per això que per millorar l'estat de l'art en els dos casos (imatges de ressonància magnètica i tomografia computeritzada) en aquesta tesi s'ha plantejat una metodologia comuna a l'hora de dissenyar i desenvolupar dos algoritmes de segmentació del fetge en les esmentades modalitats d'imatges anatòmiques. El segon pas ha estat la validació de tots dos algoritmes. En el cas d'imatges de tomografia computeritzada hi ha bases de dades públiques amb imatges segmentades manualment per experts i que la comunitat científica sol utilitzar com a nexe comú a l'hora de validar i posteriorment comparar els seus algoritmes. La validació es fa mitjançant l'obtenció de determinats coeficients de similitud entre la imatge segmentada manualment pels experts i les que ens proporciona l'algoritme. Aquesta forma de validar la precisió de l'algoritme ha estat la seguida en aquesta tesi, amb l'excepció que en el cas d'imatges de ressonància magnètica no hi ha bases de dades d'accés públic. Per això, i per a aquest cas, el que s'ha fet és la creació prèvia d'una base de dades pròpia on diferents experts radiòlegs han segmentat manualment diferents estudis de pacients amb la finalitat que puguen servir com a referència i es puga seguir la mateixa metodologia que en el cas anterior. Aquesta base de dades ha fet possible que la validació es faja en 17 estudis (amb més de 1.500 imatges), cosa que converteix la validació d'aquest mètode de segmentació del fetge en imatges de ressonància magnètica en una de les més extenses publicades fins a la data. La validació i posterior comparació han deixat patent una precisió superior al 90 \% reflectit en el coeficient de \ textit {Jaccard} i \ textit {Dice}, molt d'acord amb valors publicats per la immensa majoria d'autors en que s'ha pogut comparar. No obstant això, i en general, els algoritmes plantejats en aquesta tesi han obtingut uns criteris d'ús molt més grans, ja que en general presenten menors costos de computació, una interacció clínica quasi nul·la i una iniciació nul·la en el cas de l'algoritme de ressonància magnètica i quasi nul·la en el cas d'algoritmes de tomografia computeritzada. En aquesta tesi, també s'ha abordat un tercer punt que fa ús dels resultats obtinguts en la segmentació del fetge en imatges de ressonància magnètica. Per a això, i fent ús d'algoritmes de realitat augmentada, s'ha dissenyat i validat un estudi real innocu i no invasiu per al clínic i per al pacient on s'ha demostrat que la utilització d'aquesta tecnologia reporta més beneficis pel que fa a major precisió i menor variabilitat enfront del seu no ús en un cas concret de cirurgia amb laparoscòpia.López Mir, F. (2015). Advanced techniques in medical image segmentation of the liver [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/59428TESISPremios Extraordinarios de tesis doctoralesCompendi

Modifying Donor Organ Retrieval and Preservation to Enhance Transplant Outcomes

The last 1-2 decades have seen remarkable advances in organ procurement and preservation practices, especially with renewed enthusiasm for machine perfusion (MP) technology. However, cold static storage (CS) remains the most popular world-wide approach for the preservation of organs such as the kidneys, liver, and pancreas, largely due to its simplicity. It is clear that CS techniques have limited potential for further improvement, and will likely be supplanted and/or supplemented with MP technologies over the coming years due to the reparative, resuscitative, and assessment capabilities afforded by MP. This is especially important as we increase our utilisation of marginal and/or donation after circulatory death (DCD) organs to meet the ever-increasing demand requirements for transplantation. This dissertation explores selected aspects of abdominal organ procurement and preservation as targets for improvement and/or modification with the aim to enhance recipient transplantation outcomes. The kidney is used as a model organ for the development and exploration of MP as a means to ameliorate transplant organ ischaemia-reperfusion injury (IRI), including through the targeted delivery of anti-IRI drugs. In contrast, the optimization of CS protocols, including identification of ideal perfusion fluids and in situ perfusion routes, forms the basis for liver and pancreas transplantation work in this thesis. Such investigations are necessary to promote uniformity of practice between centres, and allow appropriate comparisons between MP and CS. The kidney MP work was guided by a systematic review and meta-analysis comparing MP and CS in the clinical and pre-clinical setting. Although hypothermic MP (HMP) was shown to enhance short-term graft outcomes, results were equivocal with respect to graft survival, especially in the DCD setting. Preliminary evidence indicated the potential superiority of normothermic MP (NMP) above HMP or CS, which may be further enhanced by using NMP as a conduit for directed drug delivery to the kidney to ameliorate IRI. We therefore developed and optimized a local NMP set-up using a series of porcine kidneys, which was then utilized to deliver the anti-IRI agent CD47-blocking antibody (αCD47Ab) in a porcine DCD model. The significant potential of this agent was initially confirmed by testing in a murine model of severe warm IRI, including its comparative efficacy to two other promising IRI agents, soluble complement receptor 1 (sCR1), and recombinant thrombomodulin, and also sCR1 in combination with αCD47Ab. αCD47Ab was successfully delivered to porcine DCD kidneys using NMP, with subsequent downstream positive impacts upon renal perfusion, and some functional and IRI-related parameters. The clinical utilisation of renal NMP has so far been limited to the UK, and this modality has not been tested in human kidneys in Australasia. Furthermore, the mechanistic basis of brief renal NMP is not entirely clear. Therefore, and as a prelude to a phase I clinical trial, NMP was tested in discarded deceased donor human kidneys. Fifteen kidneys were obtained from 10 donors, and successfully underwent NMP. NMP was especially effective for assessing and improving DCD kidneys discarded for poor macroscopic perfusion at retrieval. Flow cytometry analyses showed evidence of a massive passenger leukocyte efflux during NMP. In paired kidney analyses, one hour of NMP was shown to be superior to CS alone after simulated transplantation using ex vivo whole allogeneic blood reperfusion, in terms of renal perfusion and functional parameters. Whole transcriptome RNA sequencing revealed NMP-mediated induction of protective stress and inflammatory-related pathways, in addition to a reduction in cell death pathways. Accordingly, immunofluorescence techniques confirmed a reduction in cell death and IRI in NMP kidneys compared to their CS counterparts. CS and procurement techniques formed the basis of liver and pancreas transplantation-related studies conducted for this thesis. Firstly, we showed that blood transfusion requirements can be significantly reduced in recipients if the pancreas is retrieved using ultrasonic shears (Harmonic Scalpel), implying a reduction in procedural risk and recipient sensitization. Two systematic reviews and meta-analyses were then conducted to ascertain optimal in situ perfusion/preservation fluids, and perfusion routes, during procurement of pancreatic and hepatic allografts. There was a lack of overwhelming evidence favouring any specific preservation fluid, although University of Wisconsin solution will likely remain the solution of choice, especially for the pancreas. Furthermore, in standard criteria donors, aortic-only perfusion was found to produce equivalent liver transplant outcomes in comparison to dual (aorto-portal perfusion). However, existing studies included small patient numbers and short periods of follow-up. We therefore compared aortic and dual perfusion during liver retrieval using the Australia and New Zealand Liver Transplant Registry, which provided a much larger patient cohort with prolonged follow-up. This study confirmed the equivalence of aortic-only and dual perfusion in standard criteria liver donors, however there was also evidence indicating the superiority of dual perfusion in a subset of suboptimal/higher risk donors. Overall, this thesis expounds upon the putative benefits of NMP in kidney transplantation, including by directed drug delivery targeting the IRI cascade, and also enhances our understanding of optimal perfusion routes and preservation fluids for the liver and pancreas. The ultimate aim is to facilitate expansion of the donor pool whilst simultaneously enhancing recipient transplantation outcomes through the evidence-based implementation of technologies and techniques in a unified and coordinated manner

Multimodal Therapy of Upper Gastrointestinal Malignancies

Recent decades have seen remarkable advances in the treatment of upper gastrointestinal malignancies, i.e., adenocarcinoma and squamous cell carcinoma as well as gastrointestinal stromal and other rare tumors of the esophagus and stomach. While, historically, surgical resection has been the sole treatment for these tumors, multimodal therapies have meanwhile proven their efficacy. At present, pre- and postoperative chemotherapy and radiotherapy, targeted drug therapy, and stage-specific surgical approaches are all indispensable cornerstones of an individualized treatment for upper gastrointestinal malignancies. With such multimodal treatment, better outcomes comprising improved quality of life and prolonged survival have been achieved for patients. However, for many tumor entities and stages, the ideal combination and sequence of treatments is still being evaluated in clinical trials. Moreover, the value of novel approaches such as immunotherapy or robotic surgery remains a matter of research. In this Special Issue of Cancers, up-to-date original research, short communications, and comprehensive review articles on all modalities playing a role in the treatment of upper gastrointestinal malignancies have been published

Modulated Properties of Fully Absorbable Bicomponent Meshes

Current meshes used for soft-tissue repair are mostly composed of single component, nonabsorbable yarn constructions, limiting the ability to modulate their properties. This situation has left the majority of soft tissue repair load-bearing applications to suffer distinctly from undesirable features associated, in part, with mesh inability to (1) possess short-term stiffness to facilitate tissue stability during the development of wound strength; (2) gradually transfer the perceived mechanical load as the wound builds mechanical integrity; and (3) provide compliance with load transfer to the remodeling and maturing mesh/tissue complex. The likelihood of long-term complications is reduced for fully absorbable systems with degradation and absorption at the conclusion of their intended functional performance. The primary goal of this dissertation was to develop and characterize a fully absorbable bicomponent mesh (ABM) for hernia repair which can modulate biomechanical and physical properties to work with the expected needs of the wound healing process. The first study reviewed the current state of hernioplasty and proposed the subject device. The second study investigated different knitting technologies to establish a mesh construction which temporally modulated properties. To this end, a novel construction using warp knitting was developed where two degradable copolyester yarns with different degradation profiles were coknit into an initially interdependent knit construction. The developed knit construction provided an initial high level of structural stiffness; however, upon degradation of the fast-degrading yarn the mesh comprised of the slow-degrading yarn was liberated and affords high compliance. In the third study, the segmented, triaxial, high-glycolide copolyester used as the fast-degrading yarn was optimized to retain strength for greater than 18 days. As such, the ABM physical and biomechanical transition was designed to temporally coincide with the expected commencement of wound strength. The fourth study investigated the in vivo tissue response and integration of the developed degradable copolyester yarns in a novel construct to simulate the ABM. Results indicated a strong initial inflammatory response which resolved quickly and an integration process that produced a dense, compacted, and oriented collagen capsule around the implant during the transition phase. For the final study, the clinically-relevant biomechanical properties of two different ABM constructions were compared against traditional hernia meshes. Using a novel synthetic in vitro simulated mesh/tissue complex, the ABM were found to provide significantly greater early stability, subsequent biomechanics that approximated that of the abdominal wall, and evidence of restoring endogenous tension to the surrounding tissue. These results were in marked contrast to traditional hernia meshes which showed stress shielding and significantly greater stiffness than the abdominal wall