The IDEAL framework for surgical robotics: development, comparative evaluation and long-term monitoring.

The next generation of surgical robotics is poised to disrupt healthcare systems worldwide, requiring new frameworks for evaluation. However, evaluation during a surgical robot's development is challenging due to their complex evolving nature, potential for wider system disruption and integration with complementary technologies like artificial intelligence. Comparative clinical studies require attention to intervention context, learning curves and standardized outcomes. Long-term monitoring needs to transition toward collaborative, transparent and inclusive consortiums for real-world data collection. Here, the Idea, Development, Exploration, Assessment and Long-term monitoring (IDEAL) Robotics Colloquium proposes recommendations for evaluation during development, comparative study and clinical monitoring of surgical robots-providing practical recommendations for developers, clinicians, patients and healthcare systems. Multiple perspectives are considered, including economics, surgical training, human factors, ethics, patient perspectives and sustainability. Further work is needed on standardized metrics, health economic assessment models and global applicability of recommendations.

High resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis.

We investigated association between HLA class I and class II alleles and haplotypes, and KIR loci and their HLA class I ligands, with multiple sclerosis (MS) in 412 European American MS patients and 419 ethnically matched controls, using next-generation sequencing. The DRB1*15:01~DQB1*06:02 haplotype was highly predisposing (odds ratio (OR) = 3.98; 95% confidence interval (CI) = 3-5.31; p-value (p) = 2.22E-16), as was DRB1*03:01~DQB1*02:01 (OR = 1.63; CI = 1.19-2.24; p = 1.41E-03). Hardy-Weinberg (HW) analysis in MS patients revealed a significant DRB1*03:01~DQB1*02:01 homozyote excess (15 observed; 8.6 expected; p = 0.016). The OR for this genotype (5.27; CI = 1.47-28.52; p = 0.0036) suggests a recessive MS risk model. Controls displayed no HW deviations. The C*03:04~B*40:01 haplotype (OR = 0.27; CI = 0.14-0.51; p = 6.76E-06) was highly protective for MS, especially in haplotypes with A*02:01 (OR = 0.15; CI = 0.04-0.45; p = 6.51E-05). By itself, A*02:01 is moderately protective, (OR = 0.69; CI = 0.54-0.87; p = 1.46E-03), and haplotypes of A*02:01 with the HLA-B Thr80 Bw4 variant (Bw4T) more so (OR = 0.53; CI = 0.35-0.78; p = 7.55E-04). Protective associations with the Bw4 KIR ligand resulted from linkage disequilibrium (LD) with DRB1*15:01, but the Bw4T variant was protective (OR = 0.64; CI = 0.49-0.82; p = 3.37-04) independent of LD with DRB1*15:01. The Bw4I variant was not associated with MS. Overall, we find specific class I HLA polymorphisms to be protective for MS, independent of the strong predisposition conferred by DRB1*15:01.

Correction: High resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis.

Since the publication of this article, the authors have found that the numbers of patients and controls were reversed. This study included 412 MS patients and 419 controls. This correction applies to the Abstract, the final paragraph of the Introduction, and the first paragraph of the Materials and Methods. This was entirely a reporting error and does not impact the Results or Conclusions.

HLA Haplotype Validator for quality assessments of HLA typing.

HLA alleles are observed in specific haplotypes, due to Linkage Disequilibrium (LD) between particular alleles. Haplotype frequencies for alleles in strong LD have been established for specific ethnic groups and racial categories. Application of high-resolution HLA typing using Next Generation Sequencing (NGS) is becoming a common practice in research and clinical laboratory settings. HLA typing errors using NGS occasionally occur due to allelic sequence imbalance or misalignment. Manual inspection of HLA genotypes is labor intensive and requires an in-depth knowledge of HLA alleles and haplotypes. We developed the "HLA Haplotype Validator (HLAHapV)" software, which inspects an HLA genotype for both the presence of common and well-documented alleles and observed haplotypes. The software also reports warnings when rare alleles, or alleles that do not belong to recognized haplotypes, are found. The software validates observable haplotypes in genotype data, providing increased confidence regarding the accuracy of the HLA typing, and thus reducing the effort involved in correcting potential HLA typing errors. The HLAHapV software is a powerful tool for quality control of HLA genotypes prior to the application of downstream analyses. We demonstrate the use of the HLAHapV software for identifying unusual haplotypes, which can lead to finding potential HLA typing errors.

A novel flexible hyper-redundant surgical robot: prototype evaluation using a single incision flexible access pelvic application as a clinical exemplar.

INTRODUCTION: The flexible endoscope is increasingly being considered as a surgical tool to enable innovative natural orifice or flexible access techniques. These experiences have exposed unique advantages but also significant challenges. Major current technical drawbacks in this setting relate to uncontrolled flexibility, inaccurate sustained target localization, unreliable navigation and overall platform instability. In striving to address existing technical limitations, this paper introduces a novel flexible hyper-redundant surgical robot and evaluates its clinical potential using a focused clinical application. METHOD: To assess utility of the device within tight confines of the human pelvis or peritoneal cavity, detailed laboratory workspace analysis experiments were undertaken using a computer-simulated model that incorporated anatomical data obtained via pelvic magnetic resonance images of eight women. Ten participants executed ninety usability and reliability trials on an ex vivo simulator, before the robot was repeatedly trialled in an in vivo porcine model. RESULTS: The robot demonstrated capability of targeting >90 % of the anatomic region of interest. All 90 user trials were successfully performed without interruption or malfunction. Significant improvements in performance, time and motion were observed between first and last sets of trials (p = 0.001). In vivo feasibility testing affirmed robustness of the device when deployed within the physiological demands of a live scale appropriate model. CONCLUSION: Technologically advanced flexible operative platforms are needed to fulfil aspirations for an introductory era of flexible access surgery. This prototype is proposed as a potential future platform for robot-assisted flexible endoscopic surgery. Encouraging pre-clinical feasibility results are demonstrated for diagnostic and therapeutic applications within the pelvis.

Single-incision transumbilical levels 1 and 2 axillary lymph node dissection using a flexible endoscope in human cadaveric models.

BACKGROUND: The use of the flexible endoscope as a surgical platform potentially exposes a range of new surgical approaches and benefits yet to be fully defined. A new method using the flexible endoscope to undertake axillary dissection for breast cancer treatment is explored together with an investigation into its acceptability to the general public. METHODS: Endoscopic axillary dissection via a transumbilical approach using the flexible endoscope passed subcutaneously from the umbilicus is described for four human cadaveric axillas. A questionnaire, validated by clinicians, explored the general public's reaction to the approach and how it might be influenced by potentially serious morbidity such as an increased rate of cancer recurrence. RESULTS: All axillas were accessed successfully via the transumbilical approach. Levels 1 and 2 axillary dissection was attempted on four axillas. Scarring from previous axillary surgery prevented dissection in one case. In the remaining three cases, respectively 12, 11, and 14 lymph nodes were harvested. The operative times improved with each case, from 1080 to 390 min. A total of 127 people responded to the questionnaire, with 73 % preferring the described approach over the open and periareolar alternatives when morbidities were considered equivalent. When a hypothetical elevated risk of cancer recurrence was included with the transumbilical approach, one-fifth of the public still accepted the approach due to the likelihood of a superior cosmesis. CONCLUSION: The use of the flexible endoscope for oncologically safe levels 1 and 2 axillary dissection is possible and would be acceptable to the general public if it were clinically approved. However, significant challenges with the current endoscopic equipment and relevant instrumentation limit the potential of the technique. Technical innovation in terms of new instrument design with improved ergonomics will reduce long operating times and fatigue, thus ensuring surgical acceptance of the flexible endoscope.

Robot-assisted transvaginal peritoneoscopy using confocal endomicroscopy: a feasibility study in a porcine model.

BACKGROUND: Optical biopsy methods such as probe-based confocal laser endomicroscopy (pCLE) provide useful intraoperative real-time information, especially during minimally invasive surgery with flexible endoscopic or robotic platforms. By translating the probe at constant pressure across the target tissue, undistorted "mosaics" can be produced. However, this poses ergonomic challenges with a conventional flexible endoscope. METHODS: A 100 µm confocal depth pCLE probe was integrated into a previously described seven degrees-of-freedom articulated endoscopic robot. After estimating the average workspace created by a female pneumoperitoneum, the accessibility of the peritoneal cavity by the device for robot-assisted pCLE peritoneoscopy was calculated. To demonstrate its in vivo feasibility, the robot was inserted transvaginally in a pig, under laparoscopic vision. Optical biopsy was performed of several targets within the peritoneal cavity. RESULTS: The workspace analysis calculated that 88 % of the surface of an estimated average female pneumoperitoneum could be contacted by the probe using the robot transvaginally. In vivo, the robot was manoeuvred to provide views of all abdominal and pelvic organs. At each target there was robotic acquisition of still pCLE images, and slowly translating images for the construction of increased field-of-view mosaics up to 2 mm in length. Optical biopsies took 1-2 min per target, and at 3.5 µm lateral resolution, the mosaic images showed characteristic features of anterior abdominal wall, liver, and spleen. CONCLUSION: In the porcine model, the robotically actuated method of performing peritoneoscopy and pCLE mosaicked optical biopsy is safe and provides a consistent means of acquiring near-histological grade images of submesothelial tissue. Clinical translation is likely to provide sufficient accessibility of the peritoneal cavity.

Light sources for single-access surgery.

BACKGROUND: Minimally invasive surgical techniques such as single access and natural orifice translumenal endoscopic surgery (NOTES) aim to reduce the number of external scars on the patient but impose restrictions on the space available for the light source within the endoscope and, therefore, the size of the field of view that can be sufficiently illuminated. MATERIALS AND METHODS: This article presents and compares a number of illumination methods (xenon, light-emitting diodes, laser/phosphor, supercontinuum laser) that could be applied in single-access, robotic, and NOTES procedures. The luminance, spectral content, and intensity profile of each source was measured. Standardized images of each illuminating an abdominal simulator were assessed by a group of surgeons to provide an initial clinical impression. RESULTS: The xenon source was found to have the highest luminance when used with a standard laparoscopic light cable, but this was significantly reduced when used with a small cable suitable for single-access applications. The supercontinuum laser-based light source had brightness comparable to the xenon, which was supported by the surgical test group observations. CONCLUSIONS: The supercontinuum fiber probe is a potential alternative to xenon light sources for use in single-access surgery with its comparable luminance, small diameter, flexibility, and even illumination. An initial in vivo test is described, providing a guide for future development.

Horizon stabilized--dynamic view expansion for robotic assisted surgery (HS-DVE).

PURPOSE: New surgical approaches based on natural orifice transluminal surgery (NOTES) have the potential to further decrease morbidity and hospital stay. However, a number of key challenges have been identified preventing its clinical adoption, including inadequate instrument design and spatial disorientation. Furthermore, retroflexion, missing fixed anatomical references, and limited field-of-view are key factors contributing to disorientation in NOTES. METHODS: A hybrid approach of integrated orientation sensing and real-time vision processing is proposed to restore orientation cues for improved surgical navigation. The distal tip of an articulated robotic endoscope is equipped with an inertial measurement unit (IMU) enabling video images to be reoriented and stabilized with respect to the horizon. This is performed by measuring the direction of gravity in relation to the cameras. Dynamic view expansion is used to increase the field-of-view of the endoscope. The method registers past video images to the current image and creates an enlarged visualization of the anatomy through simultaneous localization and mapping (SLAM). RESULTS: The clinical potential of the system is demonstrated on a NOTES appendectomy procedure performed on the NOSsE phantom. This involves an articulated robotic endoscope navigating to visualize the appendix while retroflexed. The horizon stabilization is additionally evaluated quantitatively against known ground truth. CONCLUSIONS: The combination of horizon stabilization and dynamic view expansion presents a realistic approach for reintroducing orientation and navigation cues during NOTES. The platform allows real-time implementation, which is an important prerequisite for further clinical evaluation.

Design of a Multitasking Robotic Platform with Flexible Arms and Articulated Head for Minimally Invasive Surgery.

This paper describes a multitasking robotic platform for Minimally Invasive Surgery (MIS). The device is designed to be introduced through a standard trocar port. Once the device is inserted to the desired surgical site, it can be reconfigured by lifting an articulated section, and protruding two tendon driven flexible arms. Each of the arms holds an interchangeable surgical instrument. The articulated section features a 2 Degrees-of-Freedom (DoF) universal joint followed by a single DoF yaw joint. It incorporates an on-board camera and LED light source at the distal end, leaving a Ø3mm channel for an additional instrument. The main shaft of the robot is largely hollow, leaving ample space for the insertion of two tendon driven flexible arms integrated with surgical instruments. The ex-vivo and in-vivo experiments demonstrate the potential clinical value of the device for performing surgical tasks through single incision or natural orifice transluminal procedures.

A hand-held instrument to maintain steady tissue contact during probe-based confocal laser endomicroscopy.

Probe-based confocal laser endomicroscopy (pCLE) provides high-resolution in vivo imaging for intraoperative tissue characterization. Maintaining a desired contact force between target tissue and the pCLE probe is important for image consistency, allowing large area surveillance to be performed. A hand-held instrument that can provide a predetermined contact force to obtain consistent images has been developed. The main components of the instrument include a linear voice coil actuator, a donut load-cell, and a pCLE probe. In this paper, detailed mechanical design of the instrument is presented and system level modeling of closed-loop force control of the actuator is provided. The performance of the instrument has been evaluated in bench tests as well as in hand-held experiments. Results demonstrate that the instrument ensures a consistent predetermined contact force between pCLE probe tip and tissue. Furthermore, it compensates for both simulated physiological movement of the tissue and involuntary movements of the operator's hand. Using pCLE video feature tracking of large colonic crypts within the mucosal surface, the steadiness of the tissue images obtained using the instrument force control is demonstrated by confirming minimal crypt translation.

Force adaptive multi-spectral imaging with an articulated robotic endoscope.

Recent developments in optical spectroscopic techniques have permitted in vivo, in situ cellular and molecular sensing and imaging to allow for real-time tissue characterization, functional assessment, and intraoperative guidance. The small area sensed by these probes, however, presents unique challenges when attempting to obtain useful tissue information in-vivo due to the need to maintain constant distance or contact with the target, and tissue deformation. In practice, the effective area can be increased by translating the tip of the probe over the tissue surface and generating functional maps of the underlying tissue response. However, achieving such controlled motions under manual guidance is very difficult, particularly since the probe is typically passed down the instrument channel of a flexible endoscope. This paper describes a force adaptive multi-spectral imaging system integrated with an articulated robotic endoscope that allows a constant contact force to be maintained between the probe and the tissue as the robot tip is actuated across complex tissue profiles. Detailed phantom and ex-vivo tissue validation is provided.

Rolling mechanical imaging for tissue abnormality localization during minimally invasive surgery.

We describe a novel approach for the localization of tissue abnormalities during minimally invasive surgery using a force-sensitive wheeled probe. The concept is to fuse the kinaesthetic information from the wheel-tissue rolling interaction into a pseudocolor rolling mechanical image (RMI) to visualize the spatial variation of stiffness within the internal tissue structure. Since tissue abnormalities are often firmer than the surrounding organ or parenchyma, a surgeon then can localize abnormalities by analyzing the image. Initially, a testing facility for validating the concept in an ex vivo setting was developed and used to investigate rolling "wheel-tissue" interaction. A silicone soft-tissue phantom with embedded hard nodules was constructed to allow for experimental comparison between an RMI and a known soft-tissue structure. Tests have also been performed on excised porcine organs to show the efficacy of the method when applied to biological soft tissues. Results indicate that the RMI technique is particularly suited to identifying the stiffness distribution within a tissue sample, as the continuous force measurement along a given rolling trajectory provides repeatable information regarding relative variations in the normal tissue response. When compared to multiple discrete uniaxial indentations, the continuous measurement approach of RMI is shown to be more sensitive and facilitates coverage of a large area in a short period of time. Furthermore, if parametric classification of tissue properties based on a uniaxial tissue indentation model is desirable, the rolling indentation probe can be easily employed as a uniaxial indenter.