Focal Laser Ablation of Prostate Cancer: Feasibility of Magnetic Resonance Imaging-Ultrasound Fusion for Guidance.

PURPOSE: Focal laser ablation is a potential treatment in some men with prostate cancer. Currently focal laser ablation is performed by radiologists in a magnetic resonance imaging unit (in bore). We evaluated the safety and feasibility of performing focal laser ablation in a urology clinic (out of bore) using magnetic resonance imaging-ultrasound fusion for guidance. MATERIALS AND METHODS: A total of 11 men with intermediate risk prostate cancer were enrolled in this prospective, institutional review board approved pilot study. Magnetic resonance imaging-ultrasound fusion was used to guide laser fibers transrectally into regions of interest harboring intermediate risk prostate cancer. Thermal probes were inserted for real-time monitoring of intraprostatic temperatures during laser activation. Multiparametric magnetic resonance imaging (3 Tesla) was done immediately after treatment and at 6 months along with comprehensive fusion biopsy. RESULTS: Ten of 11 patients were successfully treated while under local anesthesia. Mean procedure time was 95 minutes (range 71 to 105). Posttreatment magnetic resonance imaging revealed a confined zone of nonperfusion in all 10 men. Mean zone volume was 4.3 cc (range 2.1 to 6.0). No CTCAE grade 3 or greater adverse events developed and no changes were observed in urinary or sexual function. At 6 months magnetic resonance imaging-ultrasound fusion biopsy of the treatment site showed no cancer in 3 patients, microfocal Gleason 3 + 3 in another 3 and persistent intermediate risk prostate cancer in 4. CONCLUSIONS: Focal laser ablation of prostate cancer appears safe and feasible with the patient under local anesthesia in a urology clinic using magnetic resonance imaging-ultrasound fusion for guidance and thermal probes for monitoring. Further development is necessary to refine out of bore focal laser ablation and additional studies are needed to determine appropriate treatment margins and oncologic efficacy.

Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes.

BACKGROUND: The phylum Platyhelminthes (flatworms) contains an important group of bilaterian organisms responsible for many debilitating and chronic infectious diseases of human and animal populations inhabiting the planet today. In addition to their biomedical and veterinary relevance, some platyhelminths are also frequently used models for understanding tissue regeneration and stem cell biology. Therefore, the molecular (genetic and epigenetic) characteristics that underlie trophic specialism, pathogenicity or developmental maturation are likely to be pivotal in our continued studies of this important metazoan group. Indeed, in contrast to earlier studies that failed to detect evidence of cytosine or adenine methylation in parasitic flatworm taxa, our laboratory has recently defined a critical role for cytosine methylation in Schistosoma mansoni oviposition, egg maturation and ovarian development. Thus, in order to identify whether this epigenetic modification features in other platyhelminth species or is a novelty of S. mansoni, we conducted a study simultaneously surveying for DNA methylation machinery components and DNA methylation marks throughout the phylum using both parasitic and non-parasitic representatives. RESULTS: Firstly, using both S. mansoni DNA methyltransferase 2 (SmDNMT2) and methyl-CpG binding domain protein (SmMBD) as query sequences, we illustrate that essential DNA methylation machinery components are well conserved throughout the phylum. Secondly, using both molecular (methylation specific amplification polymorphism, MSAP) and immunological (enzyme-linked immunoabsorbent assay, ELISA) methodologies, we demonstrate that representative species (Echinococcus multilocularis, Protopolystoma xenopodis, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica and Polycelis nigra) within all four platyhelminth classes (Cestoda, Monogenea, Trematoda and 'Turbellaria') contain methylated cytosines within their genome compartments. CONCLUSIONS: Collectively, these findings provide the first direct evidence for a functionally conserved and enzymatically active DNA methylation system throughout the Platyhelminthes. Defining how this epigenetic feature shapes phenotypic diversity and development within the phylum represents an exciting new area of metazoan biology.

A Novel Sensor for Tissue Mechanical Property Detection During Robotic Surgery.

Haptic feedback relays important tissue mechanical properties to surgeons during open surgery. However, this information is lost during Robot-assisted Minimally Invasive Surgery (RMIS). Here we present a proof-of-concept for a novel instrument-integrated sensor that uses fiber Bragg grating (FBG) arrays to identify tissues based on mechanical properties. Subjects were tasked with sorting tissue phantoms based on hardness. When using a conventional surgical robot, the average error for novices (N=5) and the expert user was 22.5% and 12.5% respectively. This reduced to 2.5% and 0% when sorting with direct palpation by hand. In contrast, the senorized instrument with automated analysis was able to perform the task without any error across all trials. Clinical Relevance - The proposed sensor has the potential of identifying different tissues based on mechanical properties and thus characterize tumors and other relevant structures. It is envisaged that this will improve decision making process during RMIS and also provide useful sensory information for autonomous surgery.

Methods of monitoring thermal ablation of soft tissue tumors - A comprehensive review.

Thermal ablation is a form of hyperthermia in which oncologic control can be achieved by briefly inducing elevated temperatures, typically in the range 50-80°C, within a target tissue. Ablation modalities include high intensity focused ultrasound, radiofrequency ablation, microwave ablation, and laser interstitial thermal therapy which are all capable of generating confined zones of tissue destruction, resulting in fewer complications than conventional cancer therapies. Oncologic control is contingent upon achieving predefined coagulation zones; therefore, intraoperative assessment of treatment progress is highly desirable. Consequently, there is a growing interest in the development of ablation monitoring modalities. The first section of this review presents the mechanism of action and common applications of the primary ablation modalities. The following section outlines the state-of-the-art in thermal dosimetry which includes interstitial thermal probes and radiologic imaging. Both the physical mechanism of measurement and clinical or pre-clinical performance are discussed for each ablation modality. Thermal dosimetry must be coupled with a thermal damage model as outlined in Section 4. These models estimate cell death based on temperature-time history and are inherently tissue specific. In the absence of a reliable thermal model, the utility of thermal monitoring is greatly reduced. The final section of this review paper covers technologies that have been developed to directly assess tissue conditions. These approaches include visualization of non-perfused tissue with contrast-enhanced imaging, assessment of tissue mechanical properties using ultrasound and magnetic resonance elastography, and finally interrogation of tissue optical properties with interstitial probes. In summary, monitoring thermal ablation is critical for consistent clinical success and many promising technologies are under development but an optimal solution has yet to achieve widespread adoption.

Interstitial Optical Monitoring of Focal Laser Ablation.

Focal laser ablation is a minimally invasive method of treating cancerous lesions in organs such as prostate, liver and brain. Oncologic control is achieved by inducing hyperthermia throughout the target while minimizing damage to surrounding tissue. Consequently, successful clinical outcomes are contingent upon achieving desired ablation volumes. Magnetic resonance thermometry is frequently used to monitor the formation of the induced thermal damage zone and inform the decision to terminate energy delivery. However, due to the associated cost and complexity there is growing interest in the development of alternative approaches. Here we investigate the utility of real-time interstitial interrogation of laser-tissue interaction as an inexpensive alternative monitoring modality that provides direct assessment of tissue coagulation without the need for organ specific calibration. The optical contrast mechanism was determined using a Monte Carlo model. Subsequently, four interstitial probe designs were manufactured and assessed in a tissue mimicking phantom under simultaneous magnetic resonance imaging. Finally, the optimal probe design was evaluated in ex vivo bovine muscle. It was found to be capable of providing sufficient feedback to achieve pre-defined ablation radii in the range 4-7 mm with a mean absolute error of 0.3 mm. This approach provides an inexpensive monitoring modality that may facilitate widespread adoption of focal laser ablation.

A System for Co-Registration of High-Resolution Ultrasound, Magnetic Resonance Imaging, and Whole-Mount Pathology for Prostate Cancer.

In order to evaluate the diagnostic accuracy of high-resolution ultrasound (HRUS) for detection of prostate cancer, it must be validated against whole-mount pathology. An ex-vivo HRUS scanning system was developed and tested in phantom and human tissue experiments to allow for in-plane computational co-registration of HRUS with magnetic resonance imaging (MRI) and whole-mount pathology. The system allowed for co-registration with an error of 1.9mm±1.4mm, while also demonstrating an ability to allow for lesion identification.Clinical Relevance- Using this system, a workflow can be established to co-register HRUS with MRI and pathology to allow for the diagnostic accuracy of HRUS to be determined with direct comparison to MRI.

Monitoring Focal Laser Ablation with Interstitial Fluence Probes: Monte Carlo Simulation and Phantom Validation.

Focal laser ablation offers a minimally invasive method of treating solid organ tumors via hyperthermia. Real-time monitoring of the induced tissue damage is critical for clinical success, and is typically accomplished using thermal measurements and Arrhenius models. In this manuscript, the utility of interstitial fluence probes in assessing coagulation directly in real-time was assessed through a Monte Carlo simulation and an experimental study in tissue mimicking prostate phantoms. In the simulation results, fluence increases greater than 100% were observed inside the coagulation zone, as coagulation effectively acts as a 'light trap'. Moreover, the passing of the coagulation boundary at any given point was shown to correspond with an inflection in fluence with a mean absolute difference of 0.1mm and 0.4mm observed for the simulation and phantom respectively. These results suggest that interstitial fluence probes may be capable of providing real-time feedback during focal laser ablation.

Transoral Robotic Surgical Proficiency Via Real-Time Tactile Collision Awareness System.

OBJECTIVES: In 2009, the Food and Drug Administration approved the use of the surgical robotic system for removal of benign and malignant conditions of the upper aerodigestive tract. This novel application of robotic-assisted surgery, termed transoral robotic surgery (TORS), places robotic instruments and camera system through the mouth to reach recessed areas of the pharynx and larynx. Over the successive decade, there was a rapid adoption of TORS with a surgical growth rate that continues to increase. Despite the rapid clinical acceptance, the field of TORS has not yet seen substantive changes or advances in the technical shortcomings, the lack of which has restricted objective TORS-specific surgical skills assessment as well as subsequent skills improvement efforts. One of the primary technical challenges of TORS is operating in a confined space, where the robotic system is maneuvered within the restrictive boundaries of the mouth and throat. Due to these confined boundaries of the pharynx, instruments can frequently collide with anatomic structures such as teeth and bone, producing anatomic collisions. Therefore, we hypothesized that anatomic collisions negatively impact TORS surgical performance. Secondarily, we hypothesized that avoidance of unwanted anatomic collisions could improve TORS surgical proficiency. METHODS: Design and fidelity testing for a custom TORS training platform with an integrated anatomic collision-sensing system providing real-time tactile feedback is described. Following successful platform assembly and testing, validation study using the platform was carried through prospective surgical training with trial randomization. Twenty otolaryngology-head and neck surgery residents, each trainee performing three discrete mock surgical trials (n = 60), performed the initial system validation. Ten of the 20 residents were randomized to perform the surgical trials utilizing the real-time feedback system. The remaining 10 residents were randomized to perform the surgical trials without the feedback system, although the system still could record collision data. Surgical proficiency was measured by Global Evaluative Assessment of Robotic Skills (GEARS) score, time to completion, and tumor resection scores (categorical scale ranging 0-3, describing the adequacy of resection). RESULTS: Major anatomic collisions (greater than 5N of force) negatively affected GEARS robotic skills. A mixed model analysis demonstrated that for every additional occurrence of a major collision, GEARS robotic skills assessment score would decrease by 0.29 points (P = .04). Real-time collision awareness created significantly fewer major (> 5 N) anatomic collisions with the tactile feedback system active (n = 30, mean collisions = 2.9 ± 4.2) as compared with trials without tactile feedback (n = 30, mean collisions = 12.53 ± 23.23) (P < .001). The second assessment measure of time to completion was unaffected by the presence of collisions or by the use of tactile feedback system. The third proficiency assessment was measured with tumor resection grading. Tumor resection scores was significantly (P = .02) improved with collision awareness system activated than trials without collision awareness. CONCLUSION: In order to test our primary hypothesis, a novel TORS training platform was successfully developed that provides collision force measurements including frequency, severity, and duration of anatomic collisions. Additionally, the platform was modulated to provide real-time tactile feedback of the occurrence of out-of-field collisions. Utilizing this custom platform, our hypothesis that anatomic collisions during TORS diminishes surgical performance was supported. Additionally, our secondary hypothesis that subsequent reduction of anatomic collisions improves TORS proficiency was supported by the surgical trial. Dedicated investigation to characterize the effect size and clinical impact is required in order to translate this finding into training curriculums and into clinical utilization. LEVEL OF EVIDENCE: II (Randomized trial) Laryngoscope, 130:S1-S17, 2020.

Development of a Transoral Robotic Surgery Training Platform.

Transoral robotic surgery (TORS) presents unique challenges due to difficulty manipulating surgical instruments within the tight confines of the oral cavity. Collisions between the end effectors and anatomical structures can be visualized through the endoscope; however, instrument shaft collisions are outside of the field-of-view. Acquiring the requisite skill set to minimize these collisions is challenging due to the lack of an appropriate training platform. In this paper, we present a TORS training platform with an integrated collision sensing system and real-time haptic feedback. Preliminary testing involved the recruitment of 10 Otolaryngology residents assigned to `feedback' (N=5) and `no feedback' (N=5) groups. Each trainee performed three mock surgical procedures involving the resection of a tumor from the base of the tongue. Superior surgical performance was observed in the feedback group suggesting that haptic feedback will enhance the acquisition of surgical skills.