Ex vivo virtual and 3D printing methods for evaluating an anatomy-based spinal instrumentation technique for the 12th thoracic vertebra.

INTRODUCTION: Three-dimensional printing and virtual simulation both provide useful methods of patient-specific anatomical modeling for assessing and validating surgical techniques. A combination of these two methods for evaluating the feasibility of spinal instrumentation techniques based on anatomical landmarks has not previously been investigated. MATERIALS AND METHODS: Nineteen anonymized CT scans of the thoracic spine in adult patients were acquired. Maximum pedicle width and height were recorded, and statistical analysis demonstrated normal distributions. The images were converted into standard tessellation language (STL) files, and the T12 vertebrae were anatomically segmented. The intersection of two diagonal lines drawn from the lateral and medial borders of the T12 transverse process (TP) to the lateral border of the pars and inferolateral portion of the TP was identified on both sides of each segmented vertebra. A virtual screw was created and insertion into the pedicle on each side was simulated using the proposed landmarks. The vertebral STL files were then 3D-printed, and 38 pedicles were instrumented according to the individual posterior landmarks used in the virtual investigation. RESULTS: There were no pedicle breaches using the proposed anatomical landmarks for insertion of T12 pedicle screws in the virtual simulation component. The technique was further validated by additive manufacturing of individual T12 vertebrae and demonstrated no breaches or model failures during live instrumentation using the proposed landmarks. CONCLUSIONS: Ex vivo modeling through virtual simulation and 3D printing provides a powerful and cost-effective means of replicating vital anatomical structures for investigation of complex surgical techniques.

Comparing Standard Performance and Outcome Measures in Hospitalized Pituitary Tumor Patients with Secretory versus Nonsecretory Tumors.

BACKGROUND: Patient safety indicators (PSIs) and hospital-acquired conditions (HACs) are reported quality measures. We compared their prevalence in patients with secretory and nonsecretory pituitary adenoma using the National (Nationwide) Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. METHODS: The NIS was queried for hospitalizations 2002-2014 involving pituitary adenomas. Prevalence of PSI, HAC, and 9 pituitary-related complications was determined using International Classification of Diseases, Ninth Revision codes. Patient risk factors were evaluated through multivariate analysis. RESULTS: A total of 20,743 patients with nonsecretory tumor and 3385 patients with secretory tumor were identified. Among patients with nonsecretory tumor, 3.79% experienced any PSI or HAC. Of patients with secretory tumor, 2.54% had any PSI or HAC. Before adjusting for covariation, secretory patients were less likely to have any PSI or HAC (odds ratio [OR], 0.652; P = 0.0002), experience any pituitary-related complication (OR, 0.804; P < 0.0001), have a poor outcome (hazard ratio [HR], 0.435; P < 0.0001), and die during hospitalization (HR, 0.293; P = 0.0015). Secretory patients had significantly shorter mean hospital length of stay (secretory/nonsecretory percent difference, -11.95%; P < 0.0001). However, inverse propensity score-weighted ORs comparing the groups' outcomes showed that there was no significant difference in the prevalence of any PSIs and HACs (OR, 0.963; P = 0.8570), pituitary-related complications (OR, 0.894; P = 0.1321), poor outcomes (HR, 0.990; P = 0.9287), in-hospital death (HR, 0.663; P = 0.2967), and length of stay (percent difference, -2.31%; P = 0.2967) between groups. CONCLUSIONS: Lack of significant difference in outcome measures after controlling for covariation is consistent with our finding that patients with nonsecretory tumor have more comorbidities on presentation for treatment. PSIs and HACs have limited ability to measure complications specific to pituitary tumors.

Sarcosine promotes trafficking of dendritic cells and improves efficacy of anti-tumor dendritic cell vaccines via CXC chemokine family signaling.

BACKGROUND: Dendritic cell (DC) vaccine efficacy is directly related to the efficiency of DC migration to the lymph node after delivery to the patient. We discovered that a naturally occurring metabolite, sarcosine, increases DC migration in human and murine cells resulting in significantly improved anti-tumor efficacy. We hypothesized that sarcosine induced cell migration was due to chemokine signaling. METHODS: DCs were harvested from the bone marrow of wild type C57BL/6 mice and electroporated with tumor messenger RNA (mRNA). Human DCs were isolated from peripheral blood mononuclear cells (PBMCs). DCs were treated with 20 mM of sarcosine. Antigen specific T cells were isolated from transgenic mice and injected intravenously into tumor bearing mice. DC vaccines were delivered via intradermal injection. In vivo migration was evaluated by flow cytometry and immunofluorescence microscopy. Gene expression in RNA was investigated in DCs via RT-PCR and Nanostring. RESULTS: Sarcosine significantly increased human and murine DC migration in vitro. In vivo sarcosine-treated DCs had significantly increased migration to both the lymph nodes and spleens after intradermal delivery in mice. Sarcosine-treated DC vaccines resulted in significantly improved tumor control in a B16F10-OVA tumor flank model and improved survival in an intracranial GL261-gp100 glioma model. Gene expression demonstrated an upregulation of CXCR2, CXCL3 and CXCL1 in sarcosine- treated DCs. Further metabolic analysis demonstrated the up-regulation of cyclooxygenase-1 and Pik3cg. Sarcosine induced migration was abrogated by adding the CXCR2 neutralizing antibody in both human and murine DCs. CXCR2 neutralizing antibody also removed the survival benefit of sarcosine-treated DCs in the tumor models. CONCLUSION: Sarcosine increases the migration of murine and human DCs via the CXC chemokine pathway. This platform can be utilized to improve existing DC vaccine strategies.

Freehand C2 Pedicle Screw Placement: Surgical Anatomy and Operative Technique.

We present a surgical video demonstrating the anatomy and technique of freehand C2 pedicle screw placement using a cadaveric specimen and 3-dimensional simulation software. C2 pedicle screws have been shown to augment cervical constructs and provide increased biomechanical stability compared with pars screws due to the increased length and bony purchase of pedicle screws within the pedicle and vertebral body.1 The presence of vertebral artery variations within the transverse foramen may preclude pedicle screw placement, and these should be identified on preoperative imaging. The C2 pedicle can be directly palpated at the time of screw placement, which aids screw placement in cases of deformity or trauma. A freehand technique without the use of computed tomography scan guidance or intraoperative fluoroscopy decreases radiation exposure for the operator and patient and has been shown to be safe for patient-related outcomes.2-5 Complete exposure of the C2 posterior elements is key to identifying the pedicle. The trajectory is based on direct visualization of the medial and superior pedicle borders to avoid lateral or inferior breaches into the transverse foramen. A curved probe is used for access into the vertebral body, respecting the outer cortical walls of the pedicle. The intraosseous position is confirmed with a ball-tipped probe. Fluoroscopy should be performed after screw placement to confirm proper position. By accomplishing proper exposure and understanding the anatomy of the C2 pedicle, the placement of C2 pedicle screws using a freehand technique is a safe and efficient technique for high cervical fixation.

The Neuroanatomy of Reproduction: Seeing Is Believing.

The brain is the central controller of reproduction and the menstrual cycle. Reproductive endocrinologists spend their days treating patients with perturbations in reproduction as a result of pituitary diseases and manipulate pituitary hormones to enhance fertility and quality of life. Microscopic neuroanatomical images will allow a better understanding of how a tumor in the pituitary might affect vision, or a mass in the brain might cause amenorrhea. Clinical correlations that are taught every day become much clearer once the anatomical relationships are explored. The objective of this pictorial tour is to elucidate anatomical and clinical relationships while showcasing the neuroanatomy of reproduction.

Albert L. Rhoton Jr., MD: His Philosophy and Education of Neurosurgeons.

Dr. Rhoton's key philosophies included "Keep working hard.", "Make surgery more accurate, gentle and safe", "We want perfect anatomical dissections, because we want perfect surgical operations", "Competence without compassion is worthless. Compassion without competence is meaningless", "Neurosurgeons share a great professional gift; our lives have yielded an opportunity to help mankind in a unique and exciting way" and "There is no finish line for this effort". His words reveal his passion for microneurosurgery and infinite love for humankind. Although his reknown rested on his reputation as a researcher, Dr. Rhoton was also a devoted educator. The principal aim behind the enormous amount of work he performed was that of educating neurosurgeons worldwide, so that they could be better surgeons. His work included: (1) numerous dissection courses, (2) numerous lectures and publications including about 160 original papers (3) the textbook "RHOTON" and Rhoton Collection (4) the education of 119 research fellows. The projects directed in his lab, produced the international dissemination of neuroanatomical knowledge. The ultimate goal of his microsurgical research was to improve the care of patients with neurosurgical diseases around the world. The technical contributions and humble character of Dr. Rhoton should be remembered as we care for patients.

Three-dimensional topographic fiber tract anatomy of the cerebrum.

BACKGROUND: The fiber tracts of the cerebrum may be a more important determinant of resection limits than the cortex. Better knowledge of the 3-dimensional (3-D) anatomic organization of the fiber pathways is important in planning safe and accurate surgery for lesions within the cerebrum. OBJECTIVE: To examine the topographic anatomy of fiber tracts and subcortical gray matter of the human cerebrum and their relationships with consistent cortical, ventricular, and nuclear landmarks. METHODS: Twenty-five formalin-fixed human brains and 4 whole cadaveric heads were examined by fiber dissection technique and ×6 to ×40 magnification. The fiber tracts and central core structures, including the insula and basal ganglia, were examined and their relationships captured in 3-D photography. The depth between the surface of the cortical gyri and selected fiber tracts was measured. RESULTS: The topographic relationships of the important association, projection, and commissural fasciculi within the cerebrum and superficial cortical landmarks were identified. Important landmarks with consistent relationships to the fiber tracts were the cortical gyri and sulci, limiting sulci of the insula, nuclear masses in the central core, and lateral ventricles. The fiber tracts were also organized in a consistent pattern in relation to each other. The anatomic findings are briefly compared with functional data from clinicoradiological analysis and intraoperative stimulation of fiber tracts. CONCLUSION: An understanding of the 3-D anatomic organization of the fiber tracts of the brain is essential in planning safe and accurate cerebral surgery.