Frank Pianka

In vivo accuracy assessment of a needle-based navigation system for CT-guided radiofrequency ablation of the liver.

Computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) has become a commonly used procedure in the treatment of liver tumors. One of the main challenges related to the method is the exact placement of the instrument within the lesion. To address this issue, a system was developed for computer-assisted needle placement which uses a set of fiducial needles to compensate for organ motion in real time. The purpose of this study was to assess the accuracy of the system in vivo. Two medical experts with experience in CT-guided interventions and two nonexperts used the navigation system to perform 32 needle insertions into contrasted agar nodules injected into the livers of two ventilated swine. Skin-to-target path planning and real-time needle guidance were based on preinterventional 1 mm CT data slices. The lesions were hit in 97% of all trials with a mean user error of 2.4 +/- 2.1 mm, a mean target registration error (TRE) of 2.1 +/- 1.1 mm, and a mean overall targeting error of 3.7 +/- 2.3 mm. The nonexperts achieved significantly better results than the experts with an overall error of 2.8 +/- 1.4 mm (n=16) compared to 4.5 +/- 2.7 mm (n=16). The mean time for performing four needle insertions based on one preinterventional planning CT was 57 +/- 19 min with a mean setup time of 27 min, which includes the steps fiducial insertion (24 +/- 15 min), planning CT acquisition (1 +/- 0 min), and registration (2 +/- 1 min). The mean time for path planning and targeting was 5 +/- 4 and 2 +/- 1 min, respectively. Apart from the fiducial insertion step, experts and nonexperts performed comparably fast. It is concluded that the system allows for accurate needle placement into hepatic tumors based on one planning CT and could thus enable considerable improvement to the clinical treatment standard for RFA procedures and other CT-guided interventions in the liver. To support clinical application of the method, optimization of individual system modules to reduce intervention time is proposed.

Respiratory motion compensation for CT-guided interventions in the liver

Computed tomography (CT) guided minimally invasive procedures in the liver, such as tumor biopsy and thermal ablation therapy, require precise targeting of hepatic structures that are subject to breathing motion. To facilitate needle placement, we introduced a navigation system which uses needle-shaped optically tracked navigation aids and a real-time deformation model to continuously estimate the position of a moving target. In this study, we assessed the target position estimation accuracy of our system in vitro with a custom-designed respiratory liver motion simulator. Several real-time compatible transformations were compared as a basis for the deformation model and were evaluated in a set of experiments using different arrangements of three navigation aids in two porcine and two human livers. Furthermore, we investigated different placement strategies for the case where only two needles are used for motion compensation. Depending on the transformation and the placement of the navigation aids, our system yielded a root mean square (RMS) target position estimation error in the range of 0.7 mm to 2.9 mm throughout the breathing cycle generated by the motion simulator. Affine transformations and spline transformations performed comparably well (overall RMS < 2 mm) and were considerably better than rigid transformations. When two navigation aids were used for motion compensation instead of three, a diagonal arrangement of the needles yielded the best results. This study suggests that our navigation system could significantly improve the clinical treatment standard for CT-guided interventions in the liver.

Precision targeting of liver lesions with a needle-based soft tissue navigation system

In this study, we assessed the targeting precision of a previously reported needle-based soft tissue navigation system. For this purpose, we implanted 10 2-ml agar nodules into three pig livers as tumor models, and two of the authors used the navigation system to target the center of gravity of each nodule. In order to obtain a realistic setting, we mounted the livers onto a respiratory liver motion simulator that models the human body. For each targeting procedure, we simulated the liver biopsy workflow, consisting of four steps: preparation, trajectory planning, registration, and navigation. The lesions were successfully hit in all 20 trials. The final distance between the applicator tip and the center of gravity of the lesion was determined from control computed tomography (CT) scans and was 3.5 +/- 1.1 mm on average. Robust targeting precision of this order of magnitude would significantly improve the clinical treatment standard for various CT-guided minimally invasive interventions in the liver.

On combining internal and external fiducials for liver motion compensation

This paper presents an in-vivo accuracy study on combining skin markers (external fiducials) and fiducial needles (internal fiducials) for motion compensation during liver interventions. We compared the target registration error (TRE) for different numbers of skin markers ns and fiducial needles nf, as well as for different transformation types, in two swine using the tip of an additional tracked needle as the target. During continuous breathing, nf had the greatest effect on the accuracy, yielding mean root mean square (RMS) errors of 4.8 ± 1.1 mm (nf = 0), 2.0 ± 0.9 mm (nf = 1) and 1.7 ± 0.8 mm (nf = 2) when averaged over multiple tool arrangements (n = 18, 36, 18) with ns = 4. These values correspond to error reductions of 11%, 64% and 70%, respectively, compared to the case when no motion compensation is performed, i.e., when the target position is assumed to be constant. At expiration, the mean RMS error ranged from 1.1 mm (nf = 0) to 0.8 mm (nf = 2), which is of the order of magnitude of the target displacement. Our study further indicates that the fiducial registration error (FRE) of a rigid transformation reflecting tissue motion generally correlates strongly with the TRE. Our findings could be used in practice to (1) decide on a suitable combination of fiducials for a given intervention, considering the trade-off between high accuracy and low invasiveness, and (2) provide an intra-interventional measure of confidence for the accuracy of the system based on the FRE.

Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial.

VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points – pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

Creation and establishment of a respiratory liver motion simulator for liver interventions.

Image-guided surgery and navigation have resulted from convergent developments in radiology, teletransmission, and computer science and are well-established procedures in the surgical routine in orthopedic, neurosurgery, and head-and-neck surgery. In abdominal surgery, however, these tools have gained little attraction so far. The inability to transfer the methodology from orthopedic or neurosurgery is mainly a result of intraoperative organ movement and shifting. To practice and establish navigated interventions in the liver, a custom-designed respiratory liver motion simulator was built which models the human torso and is easy to recreate. To simulate breathing motion, an explanted porcine or human liver is mounted to the diaphragm model of the simulator, and a lung ventilator causes a periodic movement of the liver along the craniocaudal axis. Additionally, the liver can be connected to a circulating pump device which simulates hepatic perfusion and provides real surgical options to establish navigated interventions and simulate management of possible complications. Respiratory motion caused by the simulator was evaluated with an optical tracking system and it was shown that in vitro movement and deformation of a liver mounted to the device are similar to the liver movements in human or porcine bodies. Based on the tests, it is concluded that the novel respiratory liver motion simulator is suitable for in vitro evaluation of navigated systems and interventional and surgical procedures.

Respiratory liver motion simulator for validating image-guided systems ex-vivo

Objective: A clinically realistic phantom incorporating respiratory motion was developed for validating image-guided systems for the liver.Materials and methods: The respiratory liver motion simulator consists of a physical human torso model which allows for an explanted human or porcine liver to be mounted adjacent to an artificial diaphragm. The apparatus can be connected to a lung ventilator for simulation of respiratory motion and is compatible with computed tomography (CT) and magnetic resonance imaging (MRI). To analyze the liver movement generated by the simulator, we examined three porcine livers mounted to the phantom and monitored their movement with a set of optically tracked fiducial needles.Results: Mean displacement between expiration and inspiration was 15.0 ± 4.7 mm, with craniocaudal movement making up the main part (14.2 ± 4.9 mm). In addition, the livers showed movement due to tissue deformation.Conclusion: The liver movement generated by the motion simulator is comparable to that of a human liver in vivo. The phantom thus provides a low-cost alternative to animal experiments for validating image-guided systems.

Prophylactic mesh placement for the PREvention of paraSTOmal hernias: The PRESTO systematic review and meta-analysis

Background Parastomal hernia (PH) is the most common complication after ostomy formation. Prophylactic mesh placement may be effective in reducing the rate of PH at the stoma site. The aims of this systematic review were to summarize the evidence with regard to the safety and effectiveness in comparison with the standard procedure without mesh placement and to identify important risk constellations. Method A systematic literature search was performed in PubMed, EMBASE and the Cochrane library with no language or date restrictions. Randomized (RCTs) and non-randomized controlled trials (nRCTs) were included. The main outcomes of interest were PH (primary outcome) rate and stoma-related complications (secondary outcomes) such as stenosis or fistula. Statistical analysis included meta-analyses of pooled data and subgroup analyses. Results Eleven trials (eight RCTs; three nRCTs) with a total of 755 patients were included. PH rate varied from 0% to 59% in the intervention and from 20% to 94% in the control group. RCTs showed a significant reduction of PH rate in the mesh group (OR 0.24; 95% CI 0.10 to 0.58, p = 0.034), whereas included nRCTs did not. No significant differences were observed in postoperative complication rates. Subgroup analyses showed superiority of non-absorbable meshes and sublay mesh positioning in open surgery. Conclusion Prophylactic mesh placement is safe and reduces PH rate. A recommendation for prophylactic non-absorbable meshes in a sublay position can be made for patients undergoing open colorectal operations with end-ostomies. Further research endeavors should focus on patient-oriented outcomes, not only PH rate, with respect to tailored treatment in specific patient populations.

In-vitro evaluation of a novel needle-based soft tissue navigation system with a respiratory liver motion simulator

In this paper, we evaluate the target position estimation accuracy of a novel soft tissue navigation system with a custom-designed respiratory liver motion simulator. The system uses a real-time deformation model to estimate the position of the target (e.g. a tumor) during a minimally invasive intervention from the location of a set of optically tracked needle-shaped navigation aids which are placed in the vicinity of the target. A respiratory liver motion simulator was developed to evaluate the performance of the system in-vitro. It allows the mounting of an explanted liver which can be moved along the longitudinal axis of a corpus model to simulate breathing motion. In order to assess the accuracy of our system we utilized an optically trackable tool as target and estimated its position continuously from the current position of the navigation aids. Four different transformation types were compared as base for the real-time deformation model: Rigid transformations, thinplate splines, volume splines, and elastic body splines. The respective root-mean-square target position estimation errors are 2.15 mm, 1.60 mm, 1.88 mm, and 1.92 mm averaged over a set of experiments obtained from a total of six navigation aid configurations in two pig livers. The error is reduced by 76.3%, 82.4%, 79.3%, and 78.8%, respectively, compared to the case when no deformation model is applied, i.e., a constant organ position is assumed throughout the breathing cycle.

Computer-Based Liver Volumetry in the Liver Perfusion Simulator

BACKGROUND An exact preoperative liver volume calculation is important prior to liver surgery and living-related liver transplantation. However, CT or MRI assessment of preoperative liver volume is associated with an estimation error of 1.2% to 36%, and little data is available on its accuracy on the segmental level. The aim of this study was to validate arterial and portal venous flow rates and gain information on liver volumetry, including liver segments, in the liver perfusion simulator and compare it to in vivo measurements in a porcine model. MATERIAL AND METHODS The arterial and portal venous flow rates and liver volumes of 10 pigs were measured in vivo and compared with the flow rates and volumes ex vivo. CT scans were performed and the volume of the liver and its lobes calculated by water displacement or computer-assistance based on the CT scans. The right lateral lobe was plasticized and reconstructed for the volume calculation. RESULTS In the liver perfusion simulator, arterial and portal venous flow rates comparable to the in vivo rates were achieved. The liver volume had a mean difference of 10.3% between in vivo and ex vivo measurements. In the liver perfusion simulator, the mean deviation in liver volume between the computer calculation and water displacement was 2.8%. On the segmental level, the Heidelberg algorithm provided an accuracy of 97.7%. CONCLUSION The liver perfusion simulator is an excellent device for studies in liver perfusion and volumetry. Furthermore, the simulator is applicable for teaching and performing interventions and surgeries in livers.