Dynamic plasma microRNAs are biomarkers for prognosis and early detection of recurrence in colorectal cancer.

BACKGROUND: Plasma microRNAs (miRNAs) are promising non-invasive biomarkers for colorectal cancer (CRC) prognosis. However, the published studies to date have yielded conflicting and inconsistent results for specific plasma miRNAs. METHODS: We have conducted a study using robust assays to assess a panel of nine miRNAs for CRC prognosis and early detection of recurrence. Plasma samples from 144 patients in a prospective CRC cohort study were collected at diagnosis, 6, 12, and 24 months after diagnosis. miRNAs were assayed by Taqman qRT-PCR to generate miRNA normalised copy numbers. RESULTS: Preoperative high plasma miRNA levels were associated with increased recurrence risk for miR-200b (HR [95% CI]=2.04 [1.00, 4.16], P=0.05), miR-203 (HR=4.2 [1.48, 11.93], P=0.007), miR-29a (HR=2.61 [1.34,5.07], P=0.005), and miR-31 (HR=4.03 [1.76, 9.24], P=0.001). Both plasma miR-31 (AUC: 0.717) and miR-29a (AUC: 0.703) could discriminate recurrence from these patients without recurrence. In addition, high levels of miR-31 during surveillance was associated with a three-fold increased risk of recurrence across all time points. Dynamic postoperative plasma miR-141 and 16 levels correlated with recurrence in the surveillance samples. CONCLUSIONS: Pre-operative plasma miR-29a, 200b, 203, and 31 are potential CRC prognosis biomarkers. In addition, dynamic postoperative miR-31, 141 and 16 levels are potential biomarkers for the early detection of recurrence during CRC surveillance.

Beyond task time: automated measurement augments fundamentals of laparoscopic skills methodology.

BACKGROUND: Laparoscopic psychomotor skills are challenging to learn and objectively evaluate. The Fundamentals of Laparoscopic Skills (FLS) program provides a popular, inexpensive, widely-studied, and reported method for evaluating basic laparoscopic skills. With an emphasis on training safety before efficiency, we present data that explore the metrics in the FLS curriculum. MATERIALS AND METHODS: A multi-institutional (n = 3) cross-sectional study enrolled subjects (n = 98) of all laparoscopic skill levels to perform FLS tasks in an instrumented box trainer. Recorded task videos were postevaluated by faculty reviewers (n = 2) blinded to subject identity using a modified Objective Structured Assessment of Technical Skills (OSATS) protocol. FLS scores were computed for each completed task and compared with demographically established skill levels (training level and number of procedures), video review scoring, and objective performance metrics including path length, economy of motion, and peak grasping force. RESULTS: Three criteria used to determine expert skill, training and experience level, blinded review of performance by faculty via OSATS, and FLS scores, disagree in establishing concurrent validity for determining "true experts" in FLS tasks. FLS-scoring exhibited near-perfect correlation with task time for all three tasks (Pearson r = 0.99, 1.00, 1.00 with P <0.00000001). FLS error penalties had negligible effect on FLS scores. Peak grasping force did not correlate with task time or FLS scores. CONCLUSIONS: FLS technical skills scores presented negligible benefit beyond the measurement of task time. FLS scoring is weighted more toward speed than precision and may not significantly address poor tissue handling skills, especially regarding excessive grasping force. Categories of experience or training level may not form a suitable basis for establishing proficiency thresholds or for construct validity studies for technical skills.

Clinical Characteristics and Outcomes of Colorectal Cancer in the ColoCare Study: Differences by Age of Onset.

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (<50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (n = 2193). We calculated descriptive statistics and assessed associations of clinicodemographic factors with age of onset using mutually-adjusted logistic regression models. Patients were on average 60 years old, with BMI of 29 kg/m2, 52% colon cancers, 21% early-onset, and presented with stage II or III (60%) disease. Early-onset patients presented with more advanced disease (stages III-IV: 63% vs. 51%, respectively), and received more neo and adjuvant treatment compared to late-onset patients, after controlling for stage (odds ratio (OR) (95% confidence interval (CI)) = 2.30 (1.82-3.83) and 2.00 (1.43-2.81), respectively). Early-onset rectal cancer patients across all stages more commonly received neoadjuvant treatment, even when not indicated as the standard of care, e.g., during stage I disease. The odds of early-onset disease were higher among never smokers and lower among overweight patients (1.55 (1.21-1.98) and 0.56 (0.41-0.76), respectively). Patients with early-onset colorectal cancer were more likely to be diagnosed with advanced stage disease, to have received systemic treatments regardless of stage at diagnosis, and were less likely to be ever smokers or overweight.

Evaluation of Secure Messaging Applications for a Health Care System: A Case Study.

OBJECTIVE: The use of text messaging in clinical care has become ubiquitous. Due to security and privacy concerns, many hospital systems are evaluating secure text messaging applications. This paper highlights our evaluation process, and offers an overview of secure messaging functionalities, as well as a framework for how to evaluate such applications. METHODS: Application functionalities were gathered through literature review, Web sites, speaking with representatives, demonstrations, and use cases. Based on similar levels of functionalities, vendors were grouped into three tiers. Essential and secondary functionalities for our health system were defined to help narrow our vendor choices. RESULTS: We stratified 19 secure messaging vendors into three tiers: basic secure communication, secure communication within an existing clinical application, and dedicated communication and collaboration systems. Our essential requirements revolved around functionalities to enhance security and communication, while advanced functionalities were mostly considered secondary. We then narrowed our list of 19 vendors to four, then created clinical use cases to rank the final vendors. DISCUSSION: When evaluating a secure messaging application, numerous factors must be considered in parallel. These include: what clinical processes to improve, archiving text messages, mobile device management, bring your own device policy, and Wi-Fi architecture. CONCLUSION: Secure messaging applications provide a Health Insurance Portability and Accountability Act (HIPAA) compliant communication platform, and also include functionality to improve clinical collaboration and workflow. We hope that our evaluation framework can be used by other health systems to find a secure messaging application that meets their needs.

Objective assessment of telesurgical robot systems: Telerobotic FLS.

The Society of American Gastrointestinal Endoscopic Surgeons (SAGES) Fundamentals of Laparoscopic Surgery (FLS) program contains curriculum that includes both a cognitive and psychomotor skills. In this research the use of FLS Block Transfer task is used to evaluate the performance of surgeons' teleoperating the University of Washington Surgical robot. The use of the FLS Trainer Box and accessories kit provides a well-defined series of tasks that can be repeated by any researchers working in the field of surgical robotics so that systems can be evaluated using a common method.

Outcomes and Quality of Life Among Men After Anal Sphincter-Sparing Transperineal Rectourethral Fistula Repair.

OBJECTIVE: To describe long-term quality of life (QOL) outcomes after rectourethral fistula (RUF) repair. RUF is a debilitating diagnosis and complex surgical dilemma with limited data regarding QOL after repair. METHODS: Patients at a tertiary referral center undergoing transperineal RUF repair 1/2009-5/2016 were analyzed. Patients were contacted by telephone to assess QOL following repair. Descriptive analysis performed of short-term surgical data (success and complications) and long-term QOL data (novel questionnaire). RESULTS: Twenty one men underwent RUF surgery with 95% success after initial repair. Fifty two percent had a history of radiation and/or ablation. Four individuals (19%) experienced a Clavien-Dindo complication within 30 days, with 3 of those being grade III+. Fifteen had postoperative urinary incontinence, of whom 73% underwent artificial urinary sphincter placement. Three previously radiated individuals underwent subsequent urethral stricture surgery. At long-term follow-up (mean 45.6 ± 27.1 months), 53% reported perineal pain, 43% reported problems related to the gracilis flap, and 80% reported urinary incontinence (primarily occasional mild leakage). Twenty one percent were unable to do the things they wanted in their daily lives, while 80% reported that surgery positively impacted their life. None would have opted for complete urinary diversion. CONCLUSION: RUF repair leads to patient satisfaction and improved QOL, despite possible residual issues such as perineal pain and urinary incontinence. Definitive RUF repair should be offered to suitable radiated and nonradiated patients.

The red DRAGON: a multi-modality system for simulation and training in minimally invasive surgery.

With the development of new technologies in surgery, minimally invasive surgery (MIS) has drastically improved the way conventional medical procedures are performed. However, a new learning curve has resulted requiring an expertise in integrating visual information with the kinematics and dynamics of the surgical tools. The Red DRAGON is a multi-modal simulator for teaching and training MIS procedures allowing one to use it with several modalities including: simulator (physical objects and virtual objects) and an animal model. The Red DRAGON system is based on a serial spherical mechanism in which all the rotation axes intersect at a single point (remote center) allowing the endoscopic tools to pivot around the MIS port. The system includes two mechanisms that incorporate two interchangeable MIS tools. Sensors are incorporated into the mechanism and the tools measure the positions and orientations of the surgical tools as well as forces and torques applied on the tools by the surgeon. The design is based on a mechanism optimization to maximize the manipulability of the mechanism in the MIS workspace. As part of a preliminary experimental protocol, five expert level surgeons performed three laparoscopic tasks--a subset of the Fundamental Laparoscopic Skill (FLS) set as a baseline for skill assessment protocols. The results provide an insight into the kinematics and dynamics of the endoscopic tools, as the underlying measures for objectively assessing MIS skills.

CIELab and sRGB color values of in vivo normal and grasped porcine liver.

Surgical simulators are excellent training tools for minimally invasive procedures but are currently lacking in realistic tissue rendering and tissue responses to manipulation. Accurate color representation of tissues may add realism to simulators and provide medically relevant information. The goal of this study was to determine feasible methods for measuring color of in vivo tissue, specifically liver, in a standardized color space. Several compressions were applied to in vivo porcine liver. Three methods were then used to determine the CIELab and/or sRGB colors of normal and damaged liver. Results suggest that there are significant differences between normal and damaged liver color.

Generalized approach for modeling minimally invasive surgery as a stochastic process using a discrete Markov model.

Minimally invasive surgery (MIS) involves a multidimensional series of tasks requiring a synthesis between visual information and the kinematics and dynamics of the surgical tools. Analysis of these sources of information is a key step in defining objective criteria for characterizing surgical performance. The Blue DRAGON is a new system for acquiring the kinematics and the dynamics of two endoscopic tools synchronized with the endoscopic view of the surgical scene. Modeling the process of MIS using a finite state model [Markov model (MM)] reveals the internal structure of the surgical task and is utilized as one of the key steps in objectively assessing surgical performance. The experimental protocol includes tying an intracorporeal knot in a MIS setup performed on an animal model (pig) by 30 surgeons at different levels of training including expert surgeons. An objective learning curve was defined based on measuring quantitative statistical distance (similarity) between MM of experts and MM of residents at different levels of training. The objective learning curve was similar to that of the subjective performance analysis. The MM proved to be a powerful and compact mathematical model for decomposing a complex task such as laparoscopic suturing. Systems like surgical robots or virtual reality simulators in which the kinematics and the dynamics of the surgical tool are inherently measured may benefit from incorporation of the proposed methodology.

Optimization of a spherical mechanism for a minimally invasive surgical robot: theoretical and experimental approaches.

With a focus on design methodology for developing a compact and lightweight minimally invasive surgery (MIS) robot manipulator, the goal of this study is progress toward a next-generation surgical robot system that will help surgeons deliver healthcare more effectively. Based on an extensive database of in-vivo surgical measurements, the workspace requirements were clearly defined. The pivot point constraint in MIS makes the spherical manipulator a natural candidate. An experimental evaluation process helped to more clearly understand the application and limitations of the spherical mechanism as an MIS robot manipulator. The best configuration consists of two serial manipulators in order to avoid collision problems. A complete kinematic analysis and optimization incorporating the requirements for MIS was performed to find the optimal link lengths of the manipulator. The results show that for the serial spherical 2-link manipulator used to guide the surgical tool, the optimal link lengths (angles) are (60 degrees, 50 degrees). A prototype 6-DOF surgical robot has been developed and will be the subject of further study.

Control system architecture for a minimally invasive surgical robot.

As the field of surgical robotics continues to evolve, it is important to keep patient safety in mind. This paper describes a safety control architecture aimed at moving an experimental system in the direction of intrinsically safe operation. The system includes safety features such as: a small number of states, Programmable Logic Controller (PLC) state transition control, active enable, brakes, E-STOP, and a surgeon foot pedal.

Hybrid analysis of a spherical mechanism for a minimally invasive surgical (MIS) robot--design concepts for multiple optimizations.

Several criteria exist for determining the optimal design for a surgical robot. This paper considers kinematic performance metrics, which reward good kinematic performance, and dynamic performance metrics, which penalize poor dynamic performance. Kinematic and dynamic metrics are considered independently, and then combined to produce hybrid metrics. For each metric, the optimal design is the one that maximizes the performance metric over a specific design space. In the case of a 2-DOF spherical mechanism for a surgical robot, the optimal design determined by kinematic metrics is a robot arm with link angles (alpha(12)=90 degrees , alpha(23)=90 degrees ). The large link angles are the most dextrous, but have the greatest risk of robot-robot or robot-patient collisions and require the largest actuators. The link lengths determined by the dynamic metrics are much shorter, which reduces the risk of collisions, but tend to place the robot in singularities much more frequently. When the hybrid metrics are used, and a restriction that the arm must be able to reach a human's entire abdomen, the optimal design is around (alpha(12)=51 degrees, alpha(23)=54 degrees). The hybrid design provides a compromise between dexterity and compactness.

Preoperative Use of Methotrexate and the Risk of Early Postoperative Complications in Patients with Inflammatory Bowel Disease.

BACKGROUND: Preoperative immunosuppressive use among patients with Crohn's disease or ulcerative colitis may lead to an increased risk of postoperative complications. There is limited information on the preoperative safety profile of methotrexate (MTX) in inflammatory bowel disease (IBD). METHODS: A retrospective study of patients who underwent abdominal surgery for IBD between 1993 and 2012 was performed and records abstracted, including preoperative use of MTX, azathioprine/6-mercaptopurine, antitumor necrosis factor, and corticosteroids. Early postoperative complications, including death, septic, and nonseptic complications were identified. A meta-analysis was also performed on the use of preoperative MTX in patients with IBD or rheumatoid arthritis. RESULTS: A total of 180 patients with IBD underwent abdominal surgery. A total of 15 patients received MTX either monotherapy or in combination therapy. Total early postoperative complications were identified in 71 (39%) patients, specifically 5 patients on oral MTX. A total of 51 cases (28%) of septic complications and 20 (11%) nonseptic. No significant association between the use of MTX and early postoperative complications was found. The odds ratio (OR) of complications versus no complications associated with MTX was 0.75 (95% CI, 0.25-2.29) and with azathioprine/6-mercaptopurine, OR 1.48 (95% CI, 0.77-2.84). The odds of a septic complication associated with MTX were 0.58 (95% CI, 0.09-3.73), and higher in azathioprine/6-mercaptopurine, OR 3.97 (95% CI, 1.03-15.3). Our meta-analysis also did not reveal an increased risk of postoperative complications in IBD or rheumatoid arthritis on preoperative MTX (OR 0.62, 95% CI, 0.34-1.15). CONCLUSIONS: Preoperative MTX use does not seem to be associated with early postoperative complications in IBD.

Does the use of a flap during abdominoperineal resection decrease pelvic wound morbidity?

We hypothesized that the use of muscle flaps, known as tissue transfer (TT), at the time of abdominoperineal resection (APR) reduces perineal wound complications. A restrospective review of patients undergoing an APR at the University of Washington (1984-2003) was conducted. Perineal wound complications and eventual wound healing were compared in patients with and without TT. Ninety-two patients (mean age, 56.6 years) underwent APR; 23.9 per cent (n = 22) had concurrent TT. Patients undergoing TT were more likely to have cancer (91% vs. 77%, P = 0.05) and radiation therapy (86% vs. 52%, P < 0.01). Operative times were nearly 2 hours longer in patients having TT (7.4 hours +/- 2.5 hours vs. 5.6 hours +/- 1.8 hours, P = 0.03), but lengths of stay were similar (13 +/- 5.9 days vs. 12 +/- 7.6 days, P = 0.5). Patients undergoing TT had a higher rate of all wound-healing complications (59% vs. 40%, P = 0.1) and major wound-healing complications (32% vs. 26%, P = 0.6). However, these differences were not statistically significant. No differences in major complications were identified in patients with and without preoperative radiation therapy (26% vs. 28%, P = 0.8). Fifteen per cent (n = 14) of all patients failed to heal wounds at 6 months, but only 9 per cent (n = 2) of patients undergoing TT failed to heal their wounds at 6 months compared with 17 per cent (n = 12) in the non-TT group (P = 0.3). After controlling for important covariates, patients undergoing TT during an APR did not have a significantly lower rate of wound complications. The impact of TT on wound healing in patients with recurrent cancer and preoperative radiation therapy is suggestive of a benefit but requires prospective investigation.

Spherical mechanism analysis of a surgical robot for minimally invasive surgery -- analytical and experimental approaches.

Recent advances in technology have led to the fusion of MIS techniques and robot devices. However, current systems are large and cumbersome. Optimizing the surgical robot mechanism will eventually lead to its integration into the operating room (OR) of the future becoming the extended presence of the surgeon and nurses in a room occupied by the patient alone. By optimizing a spherical mechanism using data collected in-vivo during MIS procedures, this study is focused on a bottom-up approach to developing a new class of surgical robotic arms while maximizing their performance and minimizing their size. The spherical mechanism is a rotational manipulator with all axes intersecting at the center of the sphere. Locating the rotation center of the mechanism at the MIS port makes this class of mechanism a suitable candidate for the first two links of a surgical robot for MIS. The required dexterous workspace (DWS) is defined as the region in which 95% of the tool motions are contained based on in-vivo measurements. The extended dexterous workspace (EDWS) is defined as the entire abdominal cavity reachable by a MIS instruments. The DWS is defined by a right circular cone with a vertex angle of 60 degrees and the EDWS is defined by a cone with an elliptical cross section created by two orthogonal vertex angles of 60 degrees and 90 degrees. A compound function based on the mechanism's isotropy and the mechanism stiffness was considered as the performance metric cost function. Optimization across both the DWS and the EDWS lead to a serial mechanism configuration with link length angles of 74 degrees and 60 degrees for a serial configuration. This mechanism configuration maximized the kinematic performance in the DWS while keeping the EDWS as its reachable workspace. Surgeons, using a mockup of two mechanisms in a MIS setup, validated these results experimentally. From these experiments the serial configuration was deemed most applicable for MIS robotic applications compared to a parallel mechanism configuration. The mechanical design of a cable actuated surgical robot was based on optimized link length angles. The system is currently being integrated into a fully operated two-arm system. Small form-factor surgical robotic arms with optimized dexterous workspaces will facilitate the integration of multiple arms while avoiding self-collision in the OR of the future.

Task decomposition of laparoscopic surgery for objective evaluation of surgical residents' learning curve using hidden Markov model.

OBJECTIVE: Evaluation of the laparoscopic surgical skills of surgical residents is usually a subjective process carried out in the operating room by senior surgeons. The two hypotheses of the current study were: (1) haptic information and tool/tissue interactions (types and transitions) performed in laparoscopic surgery are skill-dependent, and (2) statistical models (Hidden Markov Models--HMMs) incorporating these data are capable of objectively evaluating laparoscopic surgical skills. MATERIALS AND METHODS: Eight subjects (six residents--two first-year (R1), two third-year (R3), and two fifth-year (R5)--and two expert laparoscopic surgeons) performed laparoscopic cholecystectomy on pigs using an instrumented grasper equipped with force/torque (F/T) sensors at the hand/tool interface, and F/T data was synchronized with video of the operative maneuvers. Fourteen types of tool/tissue (T/T) interactions, each associated with unique F/T signatures, were defined from frame-by-frame video analysis. HMMs for each subject and step of the operation were compared to evaluate the statistical distance between expert surgeons and residents with different skill levels. RESULTS: The statistical distances between HMMs representing expert surgeons and residents were significantly different (alpha < 0.05). Major differences occurred in: (1) F/T magnitudes; (2) type of T/T interactions and transitions between them; and (3) time intervals for each T/T interaction and overall completion time. The greatest difference in performance was between R1 (junior trainee) and R3 (midlevel trainee). Smaller changes were seen as expertise increased beyond the R3 level. CONCLUSION: HMMs incorporating haptic and visual information provide an objective tool for evaluating surgical skills. Objective evidence for a "learning curve" suggests that surgical residents acquire a major portion of their laparoscopic skill between year 1 and year 3 of training.

Computer-controlled motorized endoscopic grasper for in vivo measurement of soft tissue biomechanical characteristics.

Accurate biomechanical characteristics of tissues are essential for developing realistic virtual reality surgical simulators utilizing haptic devices. Surgical simulation technology has progressed rapidly but without a large database of soft tissue mechanical properties with which to incorporate. The device described here is a computer-controlled, motorized endoscopic grasper capable of applying surgically relevant levels of force to tissue in vivo and measuring the tissue's force-deformation properties.

Quantifying surgeon grasping mechanics in laparoscopy using the Blue DRAGON system.

Mechanical testing of abdominal organs has a profound impact on surgical simulation and surgical robotics development. Due to the nonlinear and viscoelastic nature of soft tissue it is crucial to test them in surgically relevant ranges of applied force, deformation, and duration for incorporating haptic realism into surgical simulators and for safe operation of surgical robots. In order to determine these ranges, a system known as the Blue DRAGON was used to track the motions and the forces applied to surgical tools during live procedures for quantifying how surgeons typically perform a minimally invasive surgical procedure. Thirty-one surgeons of varying skill were recorded performing three different surgical tasks. Grasping force (as applied to the tool handles) and handle angle for each tool were the signals of interest among 26 channels total acquired by the system in real time. These data were analyzed for their magnitudes and frequency content. Using the tool contact state, an algorithm selected tissue grasps to analyze measures during grasps only, as well as obtain grasp durations. The mean force applied to the tool handles during tissue grasps was 8.52 N +/- 2.77 N; maximum force was 68.17 N. Ninety-five percent of the handle angle frequency content was below 1.98 Hz +/- 0.98 Hz. Average grasp time was 2.29 s +/- 1.65 s, and 95% of all grasps were held for 8.86 s +/- 7.06 s or less. The average maximum grasp time during these tasks was 13.37 s +/- 11.42 s. These results form the basis for determining how abdominal tissues are to be mechanically tested in ranges and durations of force and deformation that are surgically realistic. Additionally, this information may serve as design specifications for new surgical robots or haptic simulators.

Optimization of a vector quantization codebook for objective evaluation of surgical skill.

Surgical robotic systems and virtual reality simulators have introduced an unprecedented precision of measurement for both tool-tissue and tool-surgeon interaction; thus holding promise for more objective analyses of surgical skill. Integrative or averaged metrics such as path length, time-to-task, success/failure percentages, etc., have often been employed towards this end but these fail to address the processes associated with a surgical task as a dynamic phenomena. Stochastic tools such as Markov modeling using a 'white-box' approach have proven amenable to this type of analysis. While such an approach reveals the internal structure of the of the surgical task as a process, it requires a task decomposition based on expert knowledge, which may result in a relatively large/complex model. In this work, a 'black box' approach is developed with generalized cross-procedural applications., the model is characterized by a compact topology, abstract state definitions, and optimized codebook size. Data sets of isolated tasks were extracted from the Blue DRAGON database consisting of 30 surgical subjects stratified into six training levels. Vector quantization (VQ) was employed on the entire database, thus synthesizing a lexicon of discrete, task-independent surgical tool/tissue interactions. VQ has successfully established a dictionary of 63 surgical code words and displayed non-temporal skill discrimination. VQ allows for a more cross-procedural analysis without relying on a thorough study of the procedure, links the results of the black-box approach to observable phenomena, and reduces the computational cost of the analysis by discretizing a complex, continuous data space.