Accuracy Assessment of Pedicle and Lateral Mass Screw Insertion Assisted by Customized 3D-Printed Drill Guides:A Human Cadaver Study

BACKGROUND: Accurate cervical screw insertion is of paramount importance considering the risk of damage to adjacent vital structures. Recent research in 3-dimensional (3D) technology describes the advantage of patient-specific drill guides for accurate screw positioning, but consensus about the optimal guide design and the accuracy is lacking. OBJECTIVE: To find the optimal design and to evaluate the accuracy of individualized 3D-printed drill guides for lateral mass and pedicle screw placement in the cervical and upper thoracic spine. METHODS: Five Thiel-embalmed human cadavers were used for individualized drill-guide planning of 86 screw trajectories in the cervical and upper thoracic spine. Using 3D bone models reconstructed from acquired computed tomography scans, the drill guides were produced for both pedicle and lateral mass screw trajectories. During the study, the initial minimalistic design was refined, resulting in the advanced guide design. Screw trajectories were drilled and the realized trajectories were compared to the planned trajectories using 3D deviation analysis. RESULTS: The overall entry point and 3D angular accuracy were 0.76 +/- 0.52 mm and 3.22 +/- 2.34 degrees, respectively. Average measurements for the minimalistic guides were 1.20 mm for entry points, 5.61 degrees for the 3D angulation, 2.38 degrees for the 2D axial angulation, and 4.80 degrees for the 2D sagittal angulation. For the advanced guides, the respective measurements were 0.66 mm, 2.72 degrees, 1.26 degrees, and 2.12 degrees, respectively. CONCLUSION: The study ultimately resulted in an advanced guide design including caudally positioned hooks, crosslink support structure, and metal inlays. The novel advanced drill guide design yields excellent drilling accuracy

Accuracy of Patient-Specific 3D-Printed Drill Guides for Pedicle and Lateral Mass Screw Insertion:An Analysis of 76 Cervical and Thoracic Screw Trajectories

STUDY DESIGN: Single-center retrospective case series. OBJECTIVE: The purpose of this study was to assess the safety and accuracy of 3D-printed individualized drill guides for pedicle and lateral mass screw insertion in the cervical and upper-thoracic region, by comparing the pre-operative 3D-surgical plan with the postoperative results. SUMMARY OF BACKGROUND DATA: Posterior spinal fusion surgery can provide rigid intervertebral fixation but screw misplacement involves a high risk of neurovascular injury. However, modern spine surgeons now have tools such as virtual surgical planning and 3D-printed drill guides to facilitate spinal screw insertion. METHODS: A total of 15 patients who underwent posterior spinal fusion surgery involving patient-specific 3D-printed drill guides were included in this study. After segmentation of bone and screws, the post-operative models were superimposed onto the preoperative surgical plan. The accuracy of the realized screw trajectories was quantified by measuring the entry point and angular deviation. RESULTS: The 3D deviation analysis showed that the entry point and angular deviation over all 76 screw trajectories were 1.40 ± 0.81 mm and 6.70 ± 3.77°, respectively. Angular deviation was significantly higher in the sagittal plane than in the axial plane (P = 0.02). All screw positions were classified as 'safe' (100%), showing no neurovascular injury, facet joint violation, or violation of the pedicle wall. CONCLUSIONS: 3D virtual planning and 3D-printed patient-specific drill guides appear to be safe and accurate for pedicle and lateral mass screw insertion in the cervical and upper-thoracic spine. The quantitative 3D deviation analyses confirmed that screw positions were accurate with respect to the 3D-surgical plan. LEVEL OF EVIDENCE: 4

Operative treatment of anterior thoracic spinal cord herniation:three new cases and an individual patient data meta-analysis of 126 case reports

OBJECTIVE: Anterior thoracic spinal cord herniation is a rare cause of progressive myelopathy. Much has been speculated about the best operative treatment. However, no evidence in favor of any of the promoted techniques is available to date. Therefore, we decided to analyze treatment procedures and treatment outcomes of anterior thoracic spinal cord herniation to identify those factors that determine postoperative outcome. METHODS: An individual patient data meta-analysis was conducted, focusing on age, gender, vertebral segment of herniation, preoperative neurological status, operative interval, operative findings, operative techniques, intraoperative neurophysiological monitoring, postoperative imaging, neurological outcome and follow-up. Three cases from our own institution were added to the material collected. Bivariate analysis tests and multivariate logistic regression tests were used so as to define which variables were associated with outcome after surgical treatment of anterior thoracic spinal cord herniation. RESULTS: Brown-Séquard syndrome and release of the herniated spinal cord appeared to be strong independent factors, associated with favorable postoperative outcome. Widening of the dura defect is associated with the highest prevalence of postoperative motor function improvement when compared with the application of an anterior dura patch (P < 0.036). CONCLUSION: Most patients with anterior thoracic spinal cord herniation require operative treatment because of progressive myelopathy. Patients with Brown-Séquard syndrome have a better prognosis with respect to postoperative motor function improvement. In this review, spinal cord release and subsequent widening of the dura defect were associated with the highest prevalence of motor function improvement. D-wave recording can be a very useful tool for the surgeon during operative treatment of this disorder

Patient-Derived Papillary Thyroid Cancer Organoids for Radioactive Iodine Refractory Screening

Simple Summary Over the past three decades, the incidence of thyroid cancer has been rising, with 90% being the well-differentiated thyroid cancer subtype. After diagnosis and surgical removal of the thyroid gland, radioactive iodine is administered to induce a localized post-operative radiation treatment. However, in 15-33% of papillary thyroid cancer cases, the cells are unable to take up radioactive iodine, resulting in an ineffective treatment which sometimes has severe side effects. Pre-treatment diagnosis of non-responding patients would prevent ineffective and toxic iodine treatment. Therefore, in this study, we developed a patient-derived papillary thyroid cancer organoid model. Patient-derived organoids responding or not responding to radioactive iodine clearly resembled the tumor of origin, but showed clear differences in sodium/iodide symporter expression. Our results indicate that thyroid cancer organoids might be a suitable tool for the early diagnosis of non-responding patients, in order to eventually reduce radioactive iodine overtreatment and its many side effects for thyroid cancer patients. Patients with well-differentiated thyroid cancer, especially papillary thyroid cancer (PTC), are treated with surgical resection of the thyroid gland. This is followed by post-operative radioactive iodine (I-131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I-131, limiting further treatment options. The aim of our study was to develop a cancer organoid model with the potential for pre-treatment diagnosis of these I-131-resistant patients. PTC tissue from thirteen patients was used to establish a long-term organoid model. These organoids showed a self-renewal potential for at least five passages, suggesting the presence of cancer stem cells. We demonstrated that thyroid specific markers, a PTC marker, and transporters/receptors necessary for iodine uptake and thyroid hormone production were expressed on a gene and protein level. Additionally, we cultured organoids from I-131-resistant PTC material from three patients. When comparing PTC organoids to radioactive iodine (RAI)-refractory disease (RAIRD) organoids, a substantial discordance on both a protein and gene expression level was observed, indicating a treatment prediction potential. We showed that patient-derived PTC organoids recapitulate PTC tissue and a RAIRD phenotype. Patient-specific PTC organoids may enable the early identification of I-131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients

Establishment of the New Particle Therapy Research Center (PARTREC) at UMCG Groningen

After 25 years of successful research in the nuclear and radiation physics domain, the KVI-CART research center in Groningen is upgraded and re-established as the PARticle Therapy REsearch Center (PARTREC). Using the superconducting cyclotron AGOR and being embedded within the University Medical Center Groningen, it operates in close collaboration with the Groningen Proton Therapy Center. PARTREC uniquely combines radiation physics, medical physics, biology and radiotherapy research with an R&D program to improve hadron therapy technology and advanced radiation therapy for cancer. A number of further upgrades, scheduled for completion in 2023, will establish a wide range of irradiation modalities, such as pencil beam scanning, shoot-through with high energy protons and SOBP for protons, helium and carbon ions. Delivery of spatial fractionation (GRID) and dose rates over 300 Gy/s (FLASH) are envisioned. In addition, PARTREC delivers a variety of ion beams and infrastructure for radiation hardness experiments conducted by scientific and commercial communities, and nuclear science research in collaboration with the Faculty of Science and Engineering of the University of Groningen

Intraoperative MET-receptor targeted fluorescent imaging and spectroscopy for lymph node detection in papillary thyroid cancer:novel diagnostic tools for more selective central lymph node compartment dissection

PURPOSE: Patients undergoing prophylactic central compartment dissection (PCLND) for papillary thyroid cancer (PTC) are often overtreated. This study aimed to determine if molecular fluorescence-guided imaging (MFGI) and spectroscopy can be useful for detecting PTC nodal metastases (NM) and to identify negative central compartments intraoperatively. METHODS: We used a data-driven prioritization strategy based on transcriptomic profiles of 97 primary PTCs and 80 normal thyroid tissues (NTT) to identify tumor-specific antigens for a clinically available near-infrared fluorescent tracer. Protein expression of the top prioritized antigen was immunohistochemically validated with a tissue microarray containing primary PTC (n = 741) and NTT (n = 108). Staining intensity was correlated with 10-year locoregional recurrence-free survival (LRFS). A phase 1 study (NCT03470259) with EMI-137, targeting MET, was conducted to evaluate safety, optimal dosage for detecting PTC NM with MFGI, feasibility of NM detection with quantitative fiber-optic spectroscopy, and selective binding of EMI-137 for MET. RESULTS: MET was selected as the most promising antigen. A worse LRFS was observed in patients with positive versus negative MET staining (81.9% versus 93.2%; p = 0.02). In 19 patients, no adverse events related to EMI-137 occurred. 0.13 mg/kg EMI-137 was selected as optimal dosage for differentiating NM from normal lymph nodes using MFGI (p < 0.0001) and spectroscopy (p < 0.0001). MFGI identified 5/19 levels (26.3%) without NM. EMI-137 binds selectively to MET. CONCLUSION: MET is overexpressed in PTC and associated with increased locoregional recurrence rates. Perioperative administration of EMI-137 is safe and facilitates NM detection using MFGI and spectroscopy, potentially reducing the number of negative PCLNDs with more than 25%. CLINICAL TRIAL REGISTRATION: NCT03470259