One-Year Outcomes of the First Human Trial on Robot-Assisted Lymphaticovenous Anastomosis for Breast Cancer-Related Lymphedema.

BACKGROUND: Lymphaticovenous anastomosis, a supermicrosurgical technique, creates bypasses between the lymphatic and venous systems. The quality of lymphaticovenous anastomosis depends on the surgeon's dexterity and precision, and is subject to imperfections caused by the physiologic tremor of the human hand. A dedicated robot for microsurgery has been created to overcome these limitations (MUSA, MicroSure, Eindhoven, The Netherlands). This study describes 1-year clinical outcomes of the first-in-human trial of robot-assisted and manual lymphaticovenous anastomosis in patients with breast cancer-related lymphedema. METHODS: In this prospective pilot study, women with breast cancer-related lymphedema were randomized into the robot-assisted or manual lymphaticovenous anastomosis group. Outcomes were quality of life, arm circumference, conservative treatment frequency, arm dermal backflow stage, and anastomosis patency. RESULTS: Twenty women were included, of whom eight underwent robot-assisted lymphaticovenous anastomosis surgery and 12 underwent manual surgery. In both groups, quality of life significantly improved at 12 months (robot-assisted surgery, p = 0.045; manual surgery, p = 0.001). Arm circumference did not decrease (robot-assisted surgery, p = 0.094; manual surgery, p = 0.240). Daily use of compression garments decreased by 61.9 percent (robot-assisted surgery) and 70.2 percent (manual surgery). The frequency of manual lymphatic drainage remained similar compared with baseline. Arm dermal backflow stage was reduced in one patient in the robot-assisted group and in five cases in the manual group. Overall, 76.5 percent of the anastomoses were patent (robot-assisted surgery, 66.6 percent; manual surgery, 81.8 percent). CONCLUSIONS: After evaluating 1-year follow-up data, this study confirms the feasibility of robot-assisted lymphaticovenous anastomosis surgery. Clinical outcomes were comparable between robot-assisted and manual lymphaticovenous anastomosis. This encourages further research using the new microsurgical robot MUSA for lymphaticovenous anastomosis and other (super)microsurgical procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Reliability and Change in Erosion Measurements by High-resolution Peripheral Quantitative Computed Tomography in a Longitudinal Dataset of Rheumatoid Arthritis Patients.

OBJECTIVE: The aim of this multireader exercise was to assess the reliability and change over time of erosion measurements in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the second and third digits, blinded to time order. In total, 368 surfaces (23 patients´ 16 surfaces) were evaluated per timepoint to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light k; change over time was defined by means ± SD of erosion numbers and dimensions. RESULTS: ICC for the mean measurements of width and depth of the pathological breaks ranged between 0.819-0.883, and 0.771-0.907, respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (P = 0.0001 for erosion numbers, width, and depth in axial plane; P = 0.001 for depth in perpendicular plane). CONCLUSION: This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.

First-in-human robotic supermicrosurgery using a dedicated microsurgical robot for treating breast cancer-related lymphedema: a randomized pilot trial.

Advancements in reconstructive microsurgery have evolved into supermicrosurgery; connecting vessels with diameter between 0.3 and 0.8 mm for reconstruction of lymphatic flow and vascularized tissue transplantation. Supermicrosurgery is limited by the precision and dexterity of the surgeon's hands. Robot assistance can help overcome these human limitations, thereby enabling a breakthrough in supermicrosurgery. We report the first-in-human study of robot-assisted supermicrosurgery using a dedicated microsurgical robotic platform. A prospective randomized pilot study is conducted comparing robot-assisted and manual supermicrosurgical lymphatico-venous anastomosis (LVA) in treating breast cancer-related lymphedema. We evaluate patient outcome at 1 and 3 months post surgery, duration of the surgery, and quality of the anastomosis. At 3 months, patient outcome improves. Furthermore, a steep decline in duration of time required to complete the anastomosis is observed in the robot-assisted group (33-16 min). Here, we report the feasibility of robot-assisted supermicrosurgical anastomosis in LVA, indicating promising results for the future of reconstructive supermicrosurgery.

Robotic (super) microsurgery: Feasibility of a new master-slave platform in an in vivo animal model and future directions.

Advanced microsurgical procedures are currently limited by human precision and manual dexterity. The potential of robotics in microsurgery is highlighted, including a general overview of applications of robotic assistance in microsurgery and its introduction in different surgical specialties. A new robotic platform especially designed for (super) microsurgery is presented. Results of an in vivo animal study underline its feasibility and encourage further development toward clinical studies. Future directions of robotic microsurgery are proposed.

Development of a scoring method to visually score cortical interruptions on high-resolution peripheral quantitative computed tomography in rheumatoid arthritis and healthy controls.

OBJECTIVES: To develop a scoring method to visually score cortical interruptions in finger joints on High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), determine its intra- and inter-reader reliability and test its feasibility. METHODS: The scoring method was developed by integrating results from in-depth discussions with experts, consensus meetings, multiple reading experiments and the literature. Cortical interruptions were scored by two independent readers in an imaging dataset with finger joints from patients with rheumatoid arthritis (RA) and healthy controls and assessed for adjacent trabecular distortion. Reliability for the total number of cortical interruptions per joint and per quadrant was calculated using intraclass correlation coefficient (ICC). Feasibility was tested by recording the time to analyze one joint. RESULTS: In 98 joints we identified 252 cortical interruptions, 17% had trabecular distortion. Mean diameter of the interruptions was significantly larger in patients with RA compared with healthy controls (0.88 vs 0.47 mm, p = 0.03). Intra-reader reliability was ICC 0.88 (95% CI 0.83;0.92) per joint and ICC 0.69 (95% CI 0.65;0.73) per quadrant. Inter-reader reliability was ICC 0.48 (95% CI 0.20;0.67) per joint and ICC 0.56 (95% CI 0.49;0.62) per quadrant. The time to score one joint was mean 9.2 (SD 4.9) min. CONCLUSIONS: This scoring method allows detection of small cortical interruptions on HR-pQCT imaging of finger joints, which is promising for use in clinical studies.

Assessment of Cortical Interruptions in the Finger Joints of Patients With Rheumatoid Arthritis Using HR-pQCT, Radiography, and MRI.

Small cortical interruptions may be the first sign of an erosion, and more interruptions can be found in patients with rheumatoid arthritis (RA) compared with healthy subjects. First, we compared the number and size of interruptions in patients with RA with healthy subjects using high-resolution peripheral quantitative CT (HR-pQCT). Second, we investigated the association between structural damage and inflammatory markers on conventional radiography (CR) and MRI with interruptions on HR-pQCT. Third, the added value of HR-pQCT over CR and MRI was investigated. The finger joints of 39 patients with RA and 38 healthy subjects were examined through CR, MRI, and HR-pQCT. CRs were scored using the Sharp/Van der Heijde method. MRI images were analyzed for the presence of erosions, bone marrow edema, and synovitis. HR-pQCT images were analyzed for the number, surface area, and volume of interruptions using a semiautomated algorithm. Descriptives were calculated and associations were tested using generalized estimating equations. Significantly more interruptions and both a larger surface area and the volume of interruptions were detected in the metacarpophalangeal joints of patients with RA compared with healthy subjects (median, 2.0, 1.42 mm2 , and 0.48 mm3 versus 1.0, 0.69 mm2 , and 0.23 mm3 , respectively; all p < 0.01). Findings on CR and MRI were significantly associated with more and larger interruptions on HR-pQCT (prevalence ratios [PRs] ranging from 1.03 to 7.74; all p < 0.01) in all subjects, and were consistent in patients with RA alone. Having RA was significantly associated with more and larger interruptions on HR-pQCT (PRs, 2.33 to 5.39; all p < 0.01), also after adjustment for findings on CR or MRI. More and larger cortical interruptions were found in the finger joints of patients with RA versus healthy subjects, also after adjustment for findings on CR or MRI, implying that HR-pQCT imaging may be of value in addition to CR and MRI for the evaluation of structural damage in patients with RA. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Heterogeneity of Cortical Breaks in Hand Joints of Patients with Rheumatoid Arthritis and Healthy Controls Imaged by High-resolution Peripheral Quantitative Computed Tomography.

OBJECTIVE: Conventional radiographs (CR) of the hands are the gold standard for imaging bone erosions. The presence of bone erosions, reflected by the presence of cortical breaks, is a poor prognostic factor in patients with rheumatoid arthritis (RA). The availability of high-resolution peripheral quantitative computed tomography (HR-pQCT) enables detailed investigation of cortical breaks in rheumatic diseases. The aim of this image review is to show HR-pQCT images of the spectrum of cortical breaks with and without underlying trabecular bone changes in metacarpophalangeal (MCP) joints of healthy controls (HC) and patients with RA, with corresponding images on CR and magnetic resonance imaging (MRI). METHODS: Second and third MCP joints of 41 patients (of which 10 were early RA with ≤ 2 years and 24 longstanding RA with ≥ 10 years of disease duration) and 38 HC were imaged by CR, MRI, and HR-pQCT (XtremeCT1, Scanco Medical AG). Representative images of the spectrum of cortical breaks were selected. RESULTS: Cortical breaks were found in early and longstanding RA, but also in HC. They were heterogeneous in size, location, and number per joint, with a variety of surrounding cortical and underlying trabecular bone characteristics. CONCLUSION: Using HR-pQCT images of MCP joints, heterogeneous cortical breaks with and without surrounding trabecular bone changes were found, not only in RA but also in HC. The underlying mechanisms and significance of this spectrum of cortical breaks as found with high 3-D resolution needs further investigation.

Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution Peripheral Quantitative Computed Tomography and Interreader Reliability for Detection and Measurement.

OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) sensitively detects erosions in rheumatoid arthritis (RA); however, nonpathological cortical bone disruptions are potentially misclassified as erosive. Our objectives were to set and test a definition for pathologic cortical bone disruptions in RA and to standardize reference landmarks for measuring erosion size. METHODS: HR-pQCT images of metacarpophalangeal joints of RA and control subjects were used in an iterative process to achieve consensus on the definition and reference landmarks. Independent readers (n = 11) applied the definition to score 58 joints and measure pathologic erosions in 2 perpendicular multiplanar reformations for their maximum width and depth. Interreader reliability for erosion detection and variability in measurements between readers [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)] were calculated. RESULTS: Pathologic erosions were defined as cortical breaks extending over a minimum of 2 consecutive slices in perpendicular planes, with underlying trabecular bone loss and a nonlinear shape. Interreader agreement for classifying pathologic erosions was 90.2%, whereas variability for width and depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783). Mean erosion width was 1.84 mm (range 0.16-8.90) and mean depth was 1.86 mm (range 0.30-8.00). CONCLUSION: We propose a new definition for erosions visualized with HR-pQCT imaging. Interreader reliability for erosion detection is good, but further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued.