Robotic radical cystectomy - more precision needed?

PURPOSE OF REVIEW: Recently, several trials as well as registry-data analyses investigating the role of robot-assisted radical cystectomy with extra or intracorporal urinary diversion were completed and follow up matured. This review aims to comment on the current evidence-based findings and interpret the future role of the robotic approach as a part of the treatment of bladder cancer. RECENT FINDINGS: Numerous trials and registry-data analyses revealed no significant differences in progression-free and overall survival after open radical cystectomy or robot-assisted radical cystectomy irrespective of urinary diversion. Perioperative parameters, especially intraoperative blood loss, transfusions, thromboembolic events, wound infections and hospitalization were significantly increased in open radical cystectomy. Patients' convalescence, and especially early postsurgical quality of life, was improved by the robotic approach. The highly demanding surgery itself displayed by a flat learning curve required more than 130 surgeries per institution to reach a stable plateau of complications. The performance of high-quality radical cystectomy irrespective of the approach was significantly increased in high-volume centres. Local recurrence occurs in 11% after radical cystectomy. Current research focuses on intraoperatively usable detection methods and instruments to minimize the risk of residual tumour cells. SUMMARY: Taken together, the total intracorporal approach in radical cystectomy holds the potential to improve perioperative parameters and reduces hospitalization without impairing oncological performance of the procedure. To provide best results for the patient radical cystectomy and especially the technically challenging total intracorporal procedure will gain importance in bladder cancer treatment but should be limited to high-volume centres.

Deformable mirrors for intra-cavity use in high-power thin-disk lasers.

We present deformable mirrors for the intra-cavity use in high-power thin-disk laser resonators. The refractive power of these mirrors is continuously adaptable from -0.7 m-1 to 0.3 m-1, corresponding to radii of curvature ranging between 2.86 m (convex) and 6.67 m (concave). The optimized shape of the mirror membrane enables a very low peak-to-valley deviation from a paraboloid deformation over a large area. With the optical performance of our mirrors being equal to that of standard HR mirrors, we were able to demonstrate the tuning of the beam quality of a thin-disk laser in a range of M2 = 3 to M2 = 1 during laser operation at output powers as high as 1.1 kW.

Model-Based Characterization of Inflammatory Gene Expression Patterns of Activated Macrophages.

Macrophages are cells with remarkable plasticity. They integrate signals from their microenvironment leading to context-dependent polarization into classically (M1) or alternatively (M2) activated macrophages, representing two extremes of a broad spectrum of divergent phenotypes. Thereby, macrophages deliver protective and pro-regenerative signals towards injured tissue but, depending on the eliciting damage, may also be responsible for the generation and aggravation of tissue injury. Although incompletely understood, there is emerging evidence that macrophage polarization is critical for these antagonistic roles. To identify activation-specific expression patterns of chemokines and cytokines that may confer these distinct effects a systems biology approach was applied. A comprehensive literature-based Boolean model was developed to describe the M1 (LPS-activated) and M2 (IL-4/13-activated) polarization types. The model was validated using high-throughput transcript expression data from murine bone marrow derived macrophages. By dynamic modeling of gene expression, the chronology of pathway activation and autocrine signaling was estimated. Our results provide a deepened understanding of the physiological balance leading to M1/M2 activation, indicating the relevance of co-regulatory signals at the level of Akt1 or Akt2 that may be important for directing macrophage polarization.

Establishing and monitoring of urethral sphincter deficiency in a large animal model.

BACKGROUND: Different methods for induction and monitoring of urethral sphincter deficiency were explored in a large animal model. METHODS: Sphincter deficiency was established in female pigs by dilatation and cauterization, and amount and frequencies of voiding were monitored and explored by pad test. Sphincteric closure pressures were recorded prior to and immediately after treatment of each animal, and on day 21 by two techniques: standard urethral pressure profilometry (s-UPP) and high-definition urethral pressure profilometry (HD-UPP). Tissue samples of the urethrae were analyzed by histochemistry (AZAN- and Sirius Red staining) and by immunohistochemistry detecting desmin and fast-myosin to depict muscular tissues. RESULTS: After 3 weeks of observation animals treated by dilatation plus electrocautery presented with sphincter deficiency: measurements by both, s-UPP and HD-UPP demonstrated the maximal closure pressure reduced to baseline levels and a diminished area under the curve. Histological analyses documented, that dilatation yielded a pitted connective tissue and cauterization lead to muscle damage. Animals treated by either dilatation only or proximal injury only recovered within 3 weeks. By pad test no significant differences between untreated and treated animals or between the differently treated groups were recorded. CONCLUSION: Significant urethral sphincter deficiency can be induced in female pigs by a combination of urethral dilatation and distal electrocautery. Sphincter deficiency can be measured by standard and high-definition urethral pressure profilometry. It was maintained over 21 days after induction and correlated with visible changes in the tissue structure of the distal urethra.

Assessing the reproducibility of high definition urethral pressure profilometry and its correlation with an air-charged system.

INTRODUCTION: Recently, a new urodynamic method for the assessment of stress urinary incontinence called high definition urethral pressure profilometry (HD-UPP) has been introduced. This method combines a novel microtip catheter with advanced signal processing to enable spatial data location and the reconstruction of a pressure image inside the urethra. In order to assess the reproducibility of HD-UPP data, we statistically evaluate HD-UPP datasets and compare them to data from a double balloon air-charged system. MATERIALS AND METHODS: Both catheters are used on sedated female minipigs. Data from the microtip catheter are processed through a signal reconstruction algorithm, urodynamic features are extracted, and compared to the air-charged system. Reproducibility of HD-UPP data is assessed by statistically evaluating consecutive, intra-individual datasets. RESULTS: HD-UPP delivers results in agreement with previous comparisons of microtip and air-charged systems. The average deviation of two consecutive, intra-individual pressure images is very low at 7 cm H2 O. CONCLUSIONS: HD-UPP provides physicians with detailed information on the pressure distribution inside the urethra. Through comparison with an air-charged catheter, it is shown that HD-UPP delivers results in agreement with previous studies on the comparison of microtip and air-charged catheters. It provides excellent reproducibility, as the difference between sequentially measured profiles from the same minipig is significantly lower than the one between profiles from different minipigs.

Precise injection of human mesenchymal stromal cells in the urethral sphincter complex of Göttingen minipigs without unspecific bulking effects.

AIM: To investigate if injection of cells in the urethral sphincter complex causes unspecific bulking effects. METHODS: Human mesenchymal stromal cells were isolated, expanded, and characterized. For transurethral injection, cells were labeled with the fluorescent dye PKH26 and in magnetic resonance imaging associated experiments with superparamagnetic particles. Aliquots of cells in 250 µL solvent were injected under vision in the urethral sphincter of immuno-suppressed Göttingen minipigs. Sphincteric closure pressure was recorded by standard and high-definition urethral pressure profilometry prior to and after cell injection. The animals were sacrificed after surgery or after 3 weeks, 3, 6, or 12 months of follow-up. The localisation of the injected cells was explored by histochemistry. Sham-treated animals served as controls. RESULTS: PKH26-labeled cells survive injections in sphincter tissue samples by Williams cystoscopic injection needle well. In our animal study, the cellular depots were detected in the submucosa or in deeper zones of the sphincter, depending of the length of the injection needle (4-8 mm). Adverse effects associated with injection of cells or solvent such as a noteworthy bleeding, incontinence, or obstruction, were not recorded (n = 96 minipigs). However, a transient infiltration of macrophages was detected 3 weeks after cell injection. Changes in the urethral pressure profiles were not observed in cell-treated (n = 72) compared to sham-treated animals (n = 24). CONCLUSIONS: Injection of small aliquots of cells to investigate cell therapies in minipigs is a feasible and safe procedure, and it does not bias the intrinsic urethral wall pressure.

Improving the performance of interferometric imaging through the use of disturbance feedforward.

In this paper, we present a disturbance compensation technique to improve the performance of interferometric imaging for extremely large ground-based telescopes, e.g., the Large Binocular Telescope (LBT), which serves as the application example in this contribution. The most significant disturbance sources at ground-based telescopes are wind-induced mechanical vibrations in the range of 8-60 Hz. Traditionally, their optical effect is eliminated by feedback systems, such as the adaptive optics control loop combined with a fringe tracking system within the interferometric instrument. In this paper, accelerometers are used to measure the vibrations. These measurements are used to estimate the motion of the mirrors, i.e., tip, tilt and piston, with a dynamic estimator. Additional delay compensation methods are presented to cancel sensor network delays and actuator input delays, improving the estimation result even more, particularly at higher frequencies. Because various instruments benefit from the implementation of telescope vibration mitigation, the estimator is implemented as a separate, independent software on the telescope, publishing the estimated values via multicast on the telescope's ethernet. Every client capable of using and correcting the estimated disturbances can subscribe and use these values in a feedforward for its compensation device, e.g., the deformable mirror, the piston mirror of LINC-NIRVANA, or the fast path length corrector of the Large Binocular Telescope Interferometer. This easy-to-use approach eventually leveraged the presented technology for interferometric use at the LBT and now significantly improves the sky coverage, performance, and operational robustness of interferometric imaging on a regular basis.

High definition urethral pressure profilometry: Evaluating a novel microtip catheter.

INTRODUCTION: Urethral pressure profilometry (UPP) is used in the diagnosis of stress urinary incontinence (SUI). SUI is a significant medical, social, and economic problem, affecting about 12.5% of the population. A novel microtip catheter was developed for UPP featuring an inclination sensor and higher angular resolution compared to systems in clinical use today. Therewith, the location of each measured pressure sample can be determined and the spatial pressure distribution inside the urethra reconstructed. In order to assess the performance and plausibility of data from the microtip catheter, we compare it to data from a double balloon air charged system. MATERIALS AND METHODS: Both catheters are used on sedated female minipigs. Data from the microtip catheter are processed through a signal reconstruction algorithm, plotted and compared against data from the air-charged catheter. RESULTS: The microtip catheter delivers results in agreement with previous comparisons of microtip and air-charged systems. It additionally provides a new level of detail in the reconstructed UPPs which may lead to new insights into the sphincter mechanism of minipigs. CONCLUSIONS: The ability of air-charged catheters to measure pressure circumferentially is widely considered a main advantage over microtip catheters. However, directional pressure readings can provide additional information on angular fluctuations in the urethral pressure distribution. It is shown that the novel microtip catheter in combination with a signal reconstruction algorithm delivers plausible data. It offers the opportunity to evaluate urethral structures, especially the sphincter, in context of the correct location within the anatomical location of the pelvic floor. Neurourol. Urodynam. 35:888-894, 2016. © 2015 Wiley Periodicals, Inc.

Signal processing in urodynamics: towards high definition urethral pressure profilometry.

BACKGROUND: Urethral pressure profilometry (UPP) is used in the diagnosis of stress urinary incontinence (SUI) which is a significant medical, social, and economic problem. Low spatial pressure resolution, common occurrence of artifacts, and uncertainties in data location limit the diagnostic value of UPP. To overcome these limitations, high definition urethral pressure profilometry (HD-UPP) combining enhanced UPP hardware and signal processing algorithms has been developed. In this work, we present the different signal processing steps in HD-UPP and show experimental results from female minipigs. METHODS: We use a special microtip catheter with high angular pressure resolution and an integrated inclination sensor. Signals from the catheter are filtered and time-correlated artifacts removed. A signal reconstruction algorithm processes pressure data into a detailed pressure image on the urethra's inside. Finally, the pressure distribution on the urethra's outside is calculated through deconvolution. A mathematical model of the urethra is contained in a point-spread-function (PSF) which is identified depending on geometric and material properties of the urethra. We additionally investigate the PSF's frequency response to determine the relevant frequency band for pressure information on the urinary sphincter. RESULTS: Experimental pressure data are spatially located and processed into high resolution pressure images. Artifacts are successfully removed from data without blurring other details. The pressure distribution on the urethra's outside is reconstructed and compared to the one on the inside. Finally, the pressure images are mapped onto the urethral geometry calculated from inclination and position data to provide an integrated image of pressure distribution, anatomical shape, and location. CONCLUSIONS: With its advanced sensing capabilities, the novel microtip catheter collects an unprecedented amount of urethral pressure data. Through sequential signal processing steps, physicians are provided with detailed information on the pressure distribution in and around the urethra. Therefore, HD-UPP overcomes many current limitations of conventional UPP and offers the opportunity to evaluate urethral structures, especially the sphincter, in context of the correct anatomical location. This could enable the development of focal therapy approaches in the treatment of SUI.

In silico evaluation of geometry variations with respect to the thermal spread during coagulation of egg white using bipolar vessel sealing instruments.

BACKGROUND: Bipolar vessel sealing is an efficient electrosurgical procedure for the occlusion of blood vessels particularly during minimally invasive surgery. Reliable knowledge of the thermal spread is crucial for a safe application of bipolar vessel sealing instruments when operating close to thermo-sensitive structures, such as nerves. The evolution of the thermal spread over time and space depends on a variety of parameters, such as the biological tissue, the energy applied to the tissue, and the geometry of the vessel sealing instrument. Mathematical modeling has proven useful for the prediction of the thermal spread. It is, thus, a promising tool for the systematic analysis of the influence of geometrical changes on the thermal spread. RESULTS: We present an experimentally validated in silico study to evaluate the impact of geometry variations on the progression of chicken egg white coagulation and the final shape of coagulated egg white as an approximation of the temporal and spatial evolution of the thermal spread during bipolar vessel sealing. Egg white has similar thermal and electrical properties to human tissue, with the advantage being that the spatial and temporal evolution of the thermal spread can be visually gauged. The simulations were performed using a mathematical model based on the finite element analysis of chicken egg white. The progression of egg white coagulation was predicted for two different peak voltages and various electrode geometries. Starting with two planar electrodes, one electrode was gradually changed to adopt a wedge shape. These changes to the geometry showed a distinct influence on the progression of egg white coagulation in the simulations. The predictions were successfully validated using an experimental setup with two different electrodes representing the extreme geometries. DISCUSSION: The predicted spatial temperature distributions were experimentally validated for two geometries. Our simulation study shows that the geometry has a pronounced influence on the thermal spread and, thus, is a suitable parameter to reduce thermal damage. The in silico optimization of instrument designs is a suitable tool to accelerate the development of new vessel sealing instruments, with only a few promising designs having to be tested as prototypes.

Development of an arm support system to improve ergonomics in laparoscopic surgery: study design and provisional results.

BACKGROUND: Laparoscopic surgery (LS) induces physical stress to the surgeon that is associated with an increased prevalence of musculoskeletal pain and injury in the shoulder-neck region. The aim of this research project is to develop an arm support system (ASsyst) that reduces physical stress and is applicable to various laparoscopic interventions and operation room settings. METHODS: A systematic approach to develop an ASsyst started in October 2012 consisting of five consecutive steps. In step 1, 14 laparoscopic interventions were observed using subjective and objective measures to determine key indicators for the conception of an ASsyst in LS. In step 2, an expert workshop was held to find and evaluate solutions to generate concepts for a support system based on the results of step 1 and general methods. During the third step, prototypes of ASsyst were tested in an experimental setting. Steps 4 and 5 are currently in process and include the final development of the ASsyst using the most promising concept for the evaluation during simulated LS. RESULTS: Increased levels of physical stress were found in LS. Asymmetric strains were common. Three prototypes of ASsyst emerged from step 1 and 2. These prototypes were a cable construction with a noose for the lower arm, a support from below the elbow and a pneumatic vest supporting the upper arm. The experimental testing of these prototypes demonstrated reduced physical stress when compared to the unsupported environment. The support from below the elbow seemed to be the most practical in terms of implementation in various operation room settings and acceptance by surgeons. Step 4 and 5 are still in process. CONCLUSIONS: Ergonomic problems have been identified in LS that could be addressed by an ASsyst. The concept of supporting the elbow from below has been found to be the most promising approach.

Integration of Boolean models exemplified on hepatocyte signal transduction.

The number of mathematical models for biological pathways is rapidly growing. In particular, Boolean modelling proved to be suited to describe large cellular signalling networks. Systems biology is at the threshold to holistic understanding of comprehensive networks. In order to reach this goal, connection and integration of existing models of parts of cellular networks into more comprehensive network models is necessary. We discuss model combination approaches for Boolean models. Boolean modelling is qualitative rather than quantitative and does not require detailed kinetic information. We show that these models are useful precursors for large-scale quantitative models and that they are comparatively easy to combine. We propose modelling standards for Boolean models as a prerequisite for smooth model integration. Using these standards, we demonstrate the coupling of two logical models on two different examples concerning cellular interactions in the liver. In the first example, we show the integration of two Boolean models of two cell types in order to describe their interaction. In the second example, we demonstrate the combination of two models describing different parts of the network of a single cell type. Combination of partial models into comprehensive network models will take systems biology to the next level of understanding. The combination of logical models facilitated by modelling standards is a valuable example for the next step towards this goal.

Compensating the Influence of Tremors on Impedance Measurements Through Fourier Analysis.

Electrical mpedance measurements are a promising method for detecting structural changes in tissue and can be used in oncology to differentiate between healthy and tumorous tissue areas. The impedance measurements are so sensitive that they are not only affected by changes in the tissue itself, but also by a fluctuating contact force between sensor and tissue. In this work, the correlation between impedance measurements and movements during the measuring process, such as physiological tremors, are analyzed. To do this, impedance measurements are taken on pig bladders and the sensor-tissue contact force is simultaneously recorded. The tremor frequencies are directly visible in the Fourier transform of the impedance measurement. To counteract these effects, a Butterworth filter is used to filter out tremor frequencies and remove unwanted artefacts. Additionally, placing an spring on top of the impedance sensor helped to achieve a steadier contact force between sensor and tissue to also remove low frequency disturbances in the impedance measurements.Clinical relevance- This approach can help to obtain more reliable impedance measurements on tissue both for ex vivo and in vivo applications.

Enhancing Tissue Impedance Measurements Through Modeling of Fluid Flow During Viscoelastic Relaxation.

OBJECTIVE: Bladder cancer recurrence is an important issue after endoscopic urological surgeries. Additional sensor information such as electrical impedance measurements aim to support surgeons to ensure that the entirety of the tumor is removed. The foundation for differentiating lies in the altered sodium contents and cell structures within tumors that change their conductivity and permittivity. Mechanical deformations in the tissue expel fluid from the compressed area and pose a great difficulty, as they also lead to impedance changes. It is crucial to determine if this effect outweighs the alterations due to the tumorous tissue properties. METHODS: Impedance measurements under ongoing viscoelastic relaxation are taken on healthy and tumorous tissue samples from human bladders and breasts. A fluid model to account for extra- and intracellular fluid flow under compression is derived. It is based on the fluid content within the individual tissue compartments and their outflow via diffusion. RESULTS: After an initial deformation, the tissue relaxes and the impedance increases. The proposed model accurately represents these effects and validates the link between fluid flow under mechanical deformation and its impact on tissue impedance. A method to compensate for these undesired effects of fluid flow is proposed and the measurements are assessed in terms of differentiability between tumorous and healthy tissue samples. CONCLUSION: The electrical parameters are found to be promising for differentiation even under varying mechanical deformation, and the distinction is additionally improved by the proposed compensation approach. SIGNIFICANCE: Electrical impedance measurements show great potential to support urologist during endoscopic surgeries.

In-plane Strain Analysis by Correlating Geometry and Visual Data Through a Gradient-Based Surface Reconstruction.

Abnormalities in tissue can be detected and analyzed by evaluating mechanical properties, such as strain and stiffness. While current sensor systems are effective in measuring longitudinal properties perpendicular to the measurement sensor, identifying in-plane deformation remains a significant challenge. To address this issue, this paper presents a novel method for reconstructing in-plane deformation of observed tissue surfaces using a fringe projection sensor specifically designed for measuring tissue deformations. The method employs the latest techniques from computer vision, such as differentiable rendering, to formulate the in-plane reconstruction as a differentiable optimization problem. This enables the use of gradient-based solvers for an efficient and effective optimization of the problem optimum. Depth information and image information are combined using landmark correspondences between the respective image observations of the undeformed and deformed scenes. By comparing the reconstructed pre- and post-deformation geometry, the in-plane deformation can be revealed through the analysis of relative variations between the corresponding models' geometries. The proposed reconstruction pipeline is validated on an experimental setup, and the potential for intraoperative applications is discussed.

An Enhanced Synthetic Cystoscopic Environment for Use in Monocular Depth Estimation.

As technology advances and sensing devices improve, it is becoming more and more pertinent to ensure accurate positioning of these devices, especially within the human body. This task remains particularly difficult during manual, minimally invasive surgeries such as cystoscopies where only a monocular, endoscopic camera image is available and driven by hand. Tracking relies on optical localization methods, however, existing classical options do not function well in such a dynamic, non-rigid environment. This work builds on recent works using neural networks to learn a supervised depth estimation from synthetically generated images and, in a second training step, use adversarial training to then apply the network on real images. The improvements made to a synthetic cystoscopic environment are done in such a way to reduce the domain gap between the synthetic images and the real ones. Training with the proposed enhanced environment shows distinct improvements over previously published work when applied to real test images.

Cystoscopic depth estimation using gated adversarial domain adaptation.

Monocular depth estimation from camera images is very important for surrounding scene evaluation in many technical fields from automotive to medicine. However, traditional triangulation methods using stereo cameras or multiple views with the assumption of a rigid environment are not applicable for endoscopic domains. Particularly in cystoscopies it is not possible to produce ground truth depth information to directly train machine learning algorithms for using a monocular image directly for depth prediction. This work considers first creating a synthetic cystoscopic environment for initial encoding of depth information from synthetically rendered images. Next, the task of predicting pixel-wise depth values for real images is constrained to a domain adaption between the synthetic and real image domains. This adaptation is done through added gated residual blocks in order to simplify the network task and maintain training stability during adversarial training. Training is done on an internally collected cystoscopy dataset from human patients. The results after training demonstrate the ability to predict reasonable depth estimations from actual cystoscopic videos and added stability from using gated residual blocks is shown to prevent mode collapse during adversarial training.

Response analysis of holography-based modal wavefront sensor.

The crosstalk problem of holography-based modal wavefront sensing (HMWS) becomes more severe with increasing aberration. In this paper, crosstalk effects on the sensor response are analyzed statistically for typical aberrations due to atmospheric turbulence. For specific turbulence strength, we optimized the sensor by adjusting the detector radius and the encoded phase bias for each Zernike mode. Calibrated response curves of low-order Zernike modes were further utilized to improve the sensor accuracy. The simulation results validated our strategy. The number of iterations for obtaining a residual RMS wavefront error of 0.1λ is reduced from 18 to 3.

Geometric Mapping Evaluation for Real-Time Local Sensor Simulation.

Medical augmented reality and simulated test environments struggle in accurately simulating local sensor measurements across large spatial domains while maintaining the proper resolution of information required and real time capability. Here, a simple method for real-time simulation of intraoperative sensors is presented to aid with medical sensor development and professional training. During a surgical intervention, the interaction between medical sensor systems and tissue leads to mechanical deformation of the tissue. Through the inclusion of detailed finite element simulations in a real-time augmented reality system the method presented will allow for more accurate simulation of intraoperative sensor measurements that are independent of the mechanical state of the tissue. This concept uses a coarse, macro-level deformation mesh to maintain both computational speed and the illusion of reality and a simple geometric point mapping method to include detailed fine mesh information. The resulting system allows for flexible simulation of different types of localized sensor measurement techniques. Preliminary simulation results are provided using a real-time capable simulation environment and prove the feasibility of the method.

Detection Limits of Tetrapolar Impedance Sensors for Tissue Differentiation.

Cancer recurrence is an important issue in bladder tumor resections, because tissue cannot generously be removed from the thin bladder wall without impacting its functionality. Electrical impedance measurements during an operation aim to support the surgeon in making the decision which tissue areas to preserve, because physiological changes in tissue due to cancerous mutations can be detected by their altered electrical characteristics. This work investigates the detection limits of tetrapolar sensors when the impedance of heterogeneous tissue is measured. To do this, a finite element analysis is carried out where the sensors are placed on a dielectric medium with inclusions of different sizes, conductivity, and locations relative to the sensor. It is shown that a sensor with four electrodes in a square performs poorly in comparison to a sensor where the electrodes are symmetrically shaped as rings around one center electrode. This is mainly due to its enlarged regions of negative sensitivity. Based on the results, a third, optimized sensor geometry is proposed that shows superior performance to the other sensors in terms of geometry factor, sensitivities, and tumor detection. In simulation, it can reliably detect tumors with only half the radius of the sensor surface. Smaller tumor fractions cannot be detected by either sensor.