PROCESS VALIDATION IN CALCULATING MEDIAN PROXIMITY IN TIBIOFEMORAL CARTILAGE DEFORMATION UNDER FULL BODY LOADING

INTRODUCTION Knee osteoarthritis (OA) is characterized by progressive and irreversible degradation of tibiofemoral (TF) cartilages. Anterior cruciate ligament (ACL) rupture is a known risk factor for post-traumatic OA (PTOA) [1]. However, there are currently no in-vivo tests to diagnose pre-radiographic PTOA. Following injury, the cartilage macromolecular matrix weakens, cartilage swells and consequently cartilage softness increases [2]. This research investigates the in-vivo effects of ACL injury on cartilage deformation magnitude and rate under full body loading. The objective of this project was to determine the consequences of cartilage model mesh types and incremental mesh simplifications on the accuracy of resultant TF cartilage proximities. METHODS The affected knee of a 37 year old male PTOA subject (ACL deficient for 6 years) was imaged using Magnetic Resonance Imaging (FIESTA sequence; 3T GE Discovery 750). 3D TF bone and cartilage models were generated in Amira (VSG, Germany). The subject performed a 10 minute standing task in the Dual Fluoroscopic (DF) laboratory. DF images (32LP/mm) were collected at 6Hz. Bone alignments were reconstructed from DF images using AutoScoper (Brown University, USA) and cartilage models were co-registered. TF cartilage surface proximity was determined as the surface normal distance from each triangular mesh face onto the opposing cartilage. (Matlab, v2014b, The MathWorks, USA). The effects on surface proximities of three types of triangular cartilage surface meshes, generated in Amira, were analysed: 1) Basic Simplification - reducing face numbers with variable mesh size; 2) Remeshed Surface – isotropic mesh; 3) Iteratively Smoothed Remeshed Surface. Face numbers were reduced at 10% increments from the original surface for each surface type. RESULTS Median proximity errors for the Remeshed Surface were consistently smaller than the other mesh types across all four cartilage surface compartments. The medial tibial plateau displayed a rapid increase in error (Figure 1) indicating a high sensitivity to model simplification. This may have been due to its more complex surface geometry. The maximum acceptable error was chosen to match the minimum detectable displacement of 0.05mm for this DF system [3]. DISCUSSION AND CONCLUSIONS The findings of this investigation identified differences in the error of cartilage surface proximities under loading due to the use of different mesh types and simplifications. The smoothing technique used by Amira did not consistently converge to a surface and the variable triangle size in Basic Simplification affected the computation of proximity, resulting in unpredictable error spikes in cartilage surface proximity calculations. The results suggest that surface modeling parameters are surface geometry specific. The limiting case of the medial tibial plateau showed the optimal simplification was 0.594mm triangle mesh side length (40% of the original faces). These results inform ongoing work toward an in-vivo pre-radiographic diagnostic of PTOA

Preoperative inhibition in patients with irresectable locally advanced stage III melanoma

Aim: Neoadjuvant treatment of locally advanced disease with BRAF inhibitors is expected to increase the likelihood of a R0 resection. We present six patients with stage III unresectable melanoma, neoadjuvantly treated with BRAF inhibitors. Methods: Patients with unresectable, BRAF-mutated, stage III melanoma, were treated with BRAF inhibitors between 2012 and 2015. Unresectability was determined based on clinical and/or radiological findings. At maximal response, resection was performed. The specimen was reviewed to determine the degree of response. Results: In five of six patients a radical resection was achieved. Postoperative complications were unremarkable. In five of six resected specimens, vital tumor tissue was found. Conclusion: Neoadjuvant BRAF inhibitor treatment of locally advanced melanoma is feasible and has the potential to facilitate an R0 resection

DYNAMIC VALIDATION OF TIBIOFEMORAL KINEMATICS MEASURED USING A DUAL FLUOROSCOPY SYSTEM: A MARKER-BASED APPROACH

INTRODUCTION Knee joint cartilage degeneration in post-traumatic osteoarthritis is initiated at the point of injury and progresses through abnormal movement mechanics [1]. Anterior cruciate ligament rupture influences the development and progression of osteoarthritis [1], however the specific in vivo effects of abnormal bone and joint kinematics and kinetics on human cartilage health remain largely unknown.  Quantifying in vivo knee kinematics with submillimeter accuracies may elucidate injurious movement alterations.  Dual Fluoroscopy (DF) allows for accurate, high-speed, and non-invasive skeletal kinematics assessment, but requires validation.  The aim of this project was to quantify the in vitro accuracy and precision of a high-speed dual fluoroscopy system for measuring 6 degree of freedom (DOF) knee kinematics obtained from a marker-less 2D-3D registration approach as compared to the gold standard marker-based method. For this preliminary work, we hypothesized that the precision of inter-bead 3D Euclidean distance measurement is less than or equal to 0.10 mm [2]. METHODS Upon approval by the local ethics committee, one female cadaveric human leg was obtained through the local body donation program. Four 3mm metal beads were surgically implanted in the distal femur and proximal tibia.  Thereafter, the limb was scanned using computed tomography (CT). Following imaging, the soft tissues of the proximal shaft of the femur were dissected to expose the bone and the femoral head was removed. The proximal shaft of the femur was then fixed in a custom-made metal cylinder using fixation screws and potted using polymethyl methacrylate (PMMA). The free end of the metal cylinder was in turn fixed to an articulated 6 DOF tripod mount (Manfrotto, Italy).  In the DF laboratory the limb was suspended in the DF field of view using a custom steel frame. A rope pulley system, fixed around the ankle joint, was used to manipulate the limb. DF images were acquired at 60 Hz during manipulation of the limb into knee flexion. All images were distortion corrected and calibrated using established procedures. Marker-based tracking was conducted on 75 DF frames using in-house software to determine the 2D coordinates of the bead centroids in each image pair.  Subsequently, a modified direct linear transform was applied to obtain the 3D bead centroid coordinates. Matlab (MathWorks, v2014b, USA) code was written in order to determine the Euclidean distance between beads. RESULTSTable 1: The mean distance between beads in the femur and tibia ± SD (mm) calculated over 75 DF frames.  Right: Camera 1 DF image demonstrating the numbering of beads.DISCUSSION AND CONCLUSIONS The data indicated inter-bead distance variabilities consistent with previously observed system errors (for static imaging), when investigating a moving limb (Table 1). The observed variations could be due to multiple contributors. A lack of bead sphericity and bead deformation, as a result of surgical bead implantation, may have caused erroneous bead centroid estimates. Further, DF image distortions may have persisted even after distortion correction, contributing to observed error. Future steps include improved image calibration using a sophisticated bundle adjustment algorithm to further reduce system errors [3]

One-Year Morbidity Following Videoscopic Inguinal Lymphadenectomy for Stage III Melanoma

Simple Summary Inguinal lymphadenectomy (the removal of lymph nodes in the groin) is currently part of the treatment options for stage III melanoma patients. Surgery can be performed using one large inguinal incision (open approach) or a few smaller incisions (videoscopic approach). Previous research has already shown less severe complications and comparable oncologic outcomes after the videoscopic approach. Postoperative lymphedema following inguinal lymphadenectomy is a well-known problem which can potentially decrease quality of life. With the arrival of adjuvant systemic treatment options, less invalidating surgery is highly desirable. However, lymphedema and quality of life have only been investigated after the open approach. Therefore, we evaluated lymphedema and quality of life following videoscopic inguinal lymphadenectomy for stage III melanoma. The videoscopic inguinal lymphadenectomy is a feasible approach due to the comparable lymphedema incidence and normalization of quality of life during follow-up. Purpose: We aimed to elucidate morbidity following videoscopic inguinal lymphadenectomy for stage III melanoma. Methods: Melanoma patients who underwent a videoscopic inguinal lymphadenectomy between November 2015 and May 2019 were included. The measured outcomes were lymphedema and quality of life. Patients were reviewed one day prior to surgery and postoperatively every 3 months for one year. Results: A total number of 34 patients were included for participation; 19 (55.9%) patients underwent a concomitant iliac lymphadenectomy. Lymphedema incidence was 40% at 3 months and 50% at 12 months after surgery. Mean interlimb volume difference increased steadily from 1.8% at baseline to 6.9% at 12 months (p = 0.041). Median Lymph-ICF-LL total score increased from 0.0 at baseline to 12.0 at 3 months, and declined to 8.5 at 12 months (p = 0.007). Twelve months after surgery, Lymph-ICF-LL scores were higher for females (p = 0.021) and patients that received adjuvant radiotherapy (p = 0.013). The Median Distress Thermometer and EORTC QLQ-C30 summary score recovered to baseline at 12 months postoperatively (p = 0.747 and p = 0.203, respectively). Conclusions: The onset of lymphedema is rapid and continues to increase up to one year after videoscopic inguinal lymphadenectomy. Quality of life recovers to the baseline value

Quark mixing from softly broken symmetries

Quark flavor mixing may originate in the soft breaking of horizontal symmetries. Those symmetries, which in the simplest case are three family U(1) groups, are obeyed only by the dimension-4 Yukawa couplings and lead, when unbroken, to the absence of mixing. Their breaking may arise from the dimension-3 mass terms of SU(2)-singlet vector-like quarks. Those gauge-singlet mass terms break the horizontal symmetries at a scale much higher than the Fermi scale, yet softly, leading to quark mixing while the quark masses remain unsuppressed.Comment: 9 pages, plain Latex, no figure

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning:Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study. </p

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning:Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study. </p

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning:Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study. </p

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning:Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study. </p

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning:Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study. </p