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Ana Yoe-Cheng Chang Chan,1 Coen PM Stapper,2 Ronald LAW Bleys,3 Maarten van Leeuwen,2 Olle ten Cate4 1Department of Morphological Sciences, Faculty of Medical Sciences, National Autonomous University of Leon (UNAN-Leon), Leon, Nicaragua; 2Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands; 3Department of Anatomy, University Medical Center Utrecht, Utrecht, the Netherlands; 4Utrecht Center for Research and Development of Health Professions Education, University Medical Center Utrecht, Utrecht, the NetherlandsCorrespondence: Olle ten Cate, Utrecht Center for Research and Development of Health Professions Education, University Medical Center Utrecht, Universiteitsweg 98, 3584 CG, Utrecht, the Netherlands, Tel +31.88.75.57010, Fax +31.88.75.53409, Email T.j.tencate@umcutrecht.nlAbstract: The status of anatomy education in undergraduate medical education has dramatically changed over the course of the past century. From the most important and time-consuming component of the preclinical program, anatomy education has reduced in size and status, and yielded in curricular space to accommodate other disciplines and topics. Meanwhile, radiology has become more prominent, as a means to visualize anatomy, not only in clinical care but also in education. For this perspective paper, the authors, all with backgrounds in anatomy, radiology and/or medical education, conducted structured conversations with several academic colleagues with similar backgrounds, reviewed pertinent literature and analyzed the causes of the historical decline of a knowledge domain of medical education, that nevertheless is widely considered essential for medical students and graduates. After this analysis, the authors propose four ways forward. These directions include systematic peer teaching and development of anatomy education as a scholarly domain, further vertical integration with postgraduate medical education, full integration with radiology education, and capitalizing on educational technology. Schools in several industrialized countries have made steps in these directions, which can be further strengthened. In less affluent countries, and in countries with curricula strongly determined by tradition, these steps are less easy to make. To respond to changes in global health and health care, combined with the inevitable technological progress, and international mobility, we believe all schools will move in these directions, slower or faster.Keywords: anatomy education, radiology education, vertical integration, technology, future

Dysfunction of the facial musculature can have significant physical, social, and psychological consequences. In surgeries such as cleft surgery or craniofacial bimaxillary osteotomies, the perioral facial muscles may be detached or severed, potentially altering their functional vectors and mimicry capabilities. Ensuring correct reconstruction and maintenance of anatomical sites and muscle vectors is crucial in these procedures. However, a standardized method for perioperative assessment of the facial musculature and function is currently lacking. The aim of this study was to develop a workflow to analyse the three-dimensional vectors of the facial musculature using magnetic resonance imaging (MRI) scans. A protocol for localizing the origins and insertions of these muscles was established. The protocol was implemented using the 3DMedX computer program and tested on 7 Tesla MRI scans obtained from 10 healthy volunteers. Inter- and intra-observer variability were assessed to validate the protocol. The absolute intra-observer variability was 2.6 mm (standard deviation 2.0 mm), and absolute inter-observer variability was 2.6 mm (standard deviation 1.5 mm). This study presents a reliable and reproducible method for analysing the spatial relationships and functional significance of the facial muscles. The workflow developed facilitates perioperative assessment of the facial musculature, potentially aiding clinicians in surgical planning and potentially enhancing the outcomes of midface surgery., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To gain more insight into facial muscle function, imaging during action would be optimal. Magnetic resonance imaging is highly suitable for visualizing facial muscles. However, magnetic resonance imaging requires the individual to remain as still as possible for a while. Knowledge of the ability to sustain facial expressions is requisite before scanning individuals. This could help adapting the scanning protocol to obtain optimal quality of imaging the muscles in action. A study, including 10 healthy volunteers, was done to perceive the extent of movement while holding facial expressions of smiling and pouting. During 6 minutes, 3-dimensional photographs were taken every consecutive minute while the participants maintained their facial expressions as motionless as possible. The movement was objectified by creating distance maps between the 2 models and calculating the Root Mean Square using the software 3DMedX. The results showed that most movements occurred in the first minute, with a decrease of the intensity of the expression. After the first minute, the expression, although less intense, could be held stable. This implies that magnetic resonance imaging scanning during facial expression is possible, provided that the scanning starts after the first minute has elapsed. In addition, results demonstrated that more slackening of the muscles while smiling compared with pouting., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

Background: In 2008, members of the TEPARG provided first insights into the legal and ethical framework governing body donation in Europe. In 2012, a first update followed. This paper is now the second update on this topic and tries to extend the available information to many more European countries., Methods: For this second update, we have asked authors from all European countries to contribute their national perspectives. By this enquiry, we got many contributions compiled in this paper. When we did not get a personal contribution, one of us (EB) searched the internet for relevant information., Results: Perspectives on the legal and ethical framework governing body donation in Europe., Conclusions: We still see that a clear and rigorous legal framework is still unavailable in several countries. We found national regulations in 18 out of 39 countries; two others have at least federal laws. Several countries accept not only donated bodies but also utilise unclaimed bodies. These findings can guide policymakers in reviewing and updating existing laws and regulations related to body donation and anatomical studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: During thoracoscopic esophageal resection, while performing the supracarinal lymphadenectomy along the left recurrent laryngeal nerve (LRLN) from the aortic arch to the thoracic apex, we observed a not previously described bilayered fascia-like structure, serving as prolongation of the already known mesoesophagus., Methods: We retrospectively evaluated 70 consecutively unedited videos of thoracoscopic interventions on esophageal resections for cancer, in order to determine the validity of this finding and to describe its utility for performing a systematic and more accurate dissection of the LRLN and its adequate lymphadenectomy., Results: After mobilization of the upper esophagus from the trachea and tilting the esophagus by means of two ribbons, a bilayered fascia was observed between the esophagus and the left subclavian artery in 63 of the 70 patients included in this study. By opening the right layer, the left recurrent nerve became visualized and could be dissected free in its whole trajectory. Vessels and branches of the LRLN were divided between miniclips. Mobilizing the esophagus to the right, the base of this fascia could be found at the left subclavian artery. After dissecting and clipping the thoracic duct, complete lymphadenectomy of 2 and 4L stations could be performed. Mobilizing the esophagus in distal direction, the fascia continued at the level of the aortic arch, where it had to be divided in order to mobilize the esophagus from the left bronchus. Here, a lymphadenectomy of the aorta-pulmonary window lymph nodes (station 8) can be performed. It seems that from there the fascia continued without interruption with the previously described mesoesophagus between the thoracic aorta and the esophagus., Conclusions: Here we described the concept of the supracarinal mesoesophagus on the left side. Applying the description of the mesoesophagus will create a better understanding of the supracarinal anatomy, leading to a more adequate and reproducible surgery., (© 2023. The Author(s).)

The increasing use of three-dimensional imaging calls for reference models representing large parts of the population. The aim of this prospective study was to create templates depicting facial maturation in the younger age groups. Healthy Dutch volunteers were captured, without selection of inclusions. Three-dimensional average faces were created using MATLAB, for both genders in four age groups (4-8 years, 8-12 years, 12-16 years, and ≥16 years). Variation within the groups was calculated and depicted on an average face with a green to red colour scale, corresponding to standard deviations between 0 and ≥ 3 mm, respectively. Measurements of the distances of eight peri-oral landmarks were provided as ratios. The statistical analysis was performed using ANOVA and Tukey's test. Three-dimensional reconstructions of the average face and their first principal component were created for each gender and age group. The first principal component comprised the facial width for each group, and the variation of landmarks was low. All ratios showed an increasing trend with increasing age, except for the ratio of philtrum width to mouth width. This study is novel in comparing facial morphology by means of ratios and in creating average faces for the different young age groups. These data provide useful insights into facial maturation, which might be beneficial for facial surgeons., Competing Interests: Competing interests None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The use of an 'eversion' technique is not unequivocally proven to be superior to carotid endarterectomy with patch angioplasty. An up-to-date systematic review is needed for evaluation of benefits and harms of these two techniques., Methods: RCTs comparing eversion technique versus endarterectomy with patch angioplasty in patients with a symptomatic and significant (≥50 %) stenosis of the internal carotid artery were enrolled. Primary outcomes were all-cause mortality rate, health-related quality of life and serious adverse events. Secondary outcomes included 30-day stroke and mortality rate, (a) symptomatic arterial occlusion or restenosis, and adverse events not critical for decision making., Results: Four RCTs were included with 1272 surgical procedures for carotid stenosis; eversion technique n  = 643 and carotid endarterectomy with patch closure n  = 629. Meta-analysis comparing both techniques showed, with a very low certainty of evidence, that eversion technique might decrease the number of patients with serious adverse events (RR 0.47; 95% CI 0.34 to 0.64; p  ≤ 0.01). However, no difference was found on the other outcomes. TSA demonstrated that the required information sizes were far from being reached for these patient-important outcomes. All patient-relevant outcomes were at low certainty of evidence according to GRADE., Conclusions: This systematic review showed no conclusive evidence of any difference between eversion technique and carotid endarterectomy with patch angioplasty in carotid surgery. These conclusions are based on data obtained in trials with very low certainty according to GRADE and should therefore be interpreted cautiously. Until conclusive evidence is obtained, the standard of care according to ESVS guidelines should not be abandoned., Competing Interests: We have no conflicts of interest to disclose apart from the following: Jørn Wetterslev, MD, PhD was a member of the taskforce at Copenhagen Trial Unit (CTU) to develop theory and software for doing Trial Sequential Analysis (TSA) currently freeware available including a manual at www.ctu/tsa., (© 2023 The Authors.)

Introduction: The aim of this proof of concept human cadaver study was to quantify the effect of a bilateral extending pelvic osteotomy (BEPO) on pelvic incidence (PI) as a potential alternative for a pedicle subtraction osteotomy (PSO) in patients with severe spinal sagittal malalignment., Materials and Methods: 10 fresh frozen human cadavers were treated with the BEPO technique. CT images were made before and after the osteotomy and pure sagittal images were created on which PI was measured., Results: The mean pre-osteotomy PI was 47.9° (range 36.4-63.9) and the mean post-osteotomy PI was 36.5° (range 22.1-54.4). The mean correction was - 10.4° with a range of - 8.4° to - 17.3° (p = 0.03), which resulted in a mean decrease of 23% in the PI (range 16-42)., Conclusions: There was a feasible and effective correction of PI using the BEPO technique on the os ilium. This was a preliminary cadaveric study. No conclusions could be made on global sagittal alignment. We postulate that an extending osteotomy of the ilium could be a potential alternative for a PSO reducing the complexity of spine surgery in patients with severe spinal sagittal malalignment., (© 2022. The Author(s).)

Objective: To find out whether the vomeronasal organ (VNO) can be identified in the nose as a mucosal pit in the anterior nasal septum, to elucidate its function in man and to determine whether it is important to preserve the VNO during septal surgery., Methods: Literature review., Results and Conclusion: The VNO is histologically present in almost all humans, but a macroscopically visible septal pit does not necessarily correspond with the actual VNO. The human VNO is probably a vestigial organ with a non-operational sensory function. It is not necessary to take particular care not to damage the VNO during septal surgery., (© 2023. The Author(s).)

Background: Transcervical esophagectomy allows for esophagectomy through transcervical access and bypasses the thoracic cavity, thereby eliminating single lung ventilation. A challenging surgical approach demands thorough understanding of the encountered anatomy. This study aims to provide a comprehensive overview of surgical anatomy encountered during the (robot-assisted) minimally invasive transcervical esophagectomy (RACE and MICE)., Methods: To assess the surgical anatomy of the lower neck and mediastinum, MR images were made of a body donor after, which it was sliced at 24-μm intervals with a cryomacrotome. Images were made every 3 slices resulting in 3.200 images of which a digital 3D multiplanar reconstruction was made. For macroscopic verification, microscopic slices were made and stained every 5 mm (Mallory-Cason). Schematic drawings were made of the 3D reconstruction to demonstrate the course of essential anatomical structures in the operation field and identify anatomical landmarks., Results: Surgical anatomy 'boxes' of three levels (superior thoracic aperture, upper mediastinum, subcarinal) were created. Four landmarks were identified: (i) the course of the thoracic duct in the mediastinum; (ii) the course of the left recurrent laryngeal nerve; (iii) the crossing of the azygos vein right and dorsal of the esophagus; and (iv) the position of the aortic arch, the pulmonary arteries, and veins., Conclusions: The presented 3D reconstruction of unmanipulated human anatomy and schematic 3D 'boxes' provide a comprehensive overview of the surgical anatomy during the RACE or MICE. Our findings provide a useful tool to aid surgeons in learning the complex anatomy of the mediastinum and the exploration of new surgical approaches such as the RACE or MICE., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Facial expressions are ubiquitous in communication. Therefore, assessment of mimic function is essential in facial surgery, but no reference standards are currently available. This prospective study aims to create reference values of three-dimensional landmark displacement for different sex and age groups., Methods: Three-dimensional photographs were taken from healthy subjects in rest, maximum closed smile, and pouting. Displacement for both exercises of perioral landmarks was analyzed with MATLAB as absolute displacement and as the ratio of mouth width. Additionally, displacement in three planes was analyzed for each landmark. Averages were calculated for both genders in four age groups: 4-8, 8-12, 12-16, and >16 years., Results: In total, 328 subjects were included. Oral landmarks predominantly moved forward and backward for both exercises. Nasal landmarks predominantly moved vertically. Growing up, oral landmark displacement decreased for smiling, whereas nasal landmark displacement increased. For pouting, oral landmark displacement increased while growing up, whereas nasal landmark displacement decreased., Conclusions: The present study creates reference values for movement of perioral structures for different sex and age groups, for two facial expressions. These data are of great value for the assessment of mimic function and give insight into the development of facial animation over time., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Purpose: Degenerative changes of the lumbar spine lead in general to decrease of lumbar lordosis (LL). This change affects the overall balance of the spine, and when surgery is deemed, necessary restoration of the LL is considered. How this restoration can be achieved is a matter of controversy. The main purpose of this cadaveric study was to investigate the different steps of common posterior surgical techniques to understand the contribution of each successive step in restoring LL., Methods: Ten fresh-frozen human lumbar spine specimens were used to perform a sequential correction and instrumentation with a pedicle screw construct., Results: The mean LL angle measured at L3-L4 in intact condition was 12.9°; after screw insertion and compression, this increased to 13.8° (+ 7%, p = 0.04), after bilateral facetectomy to 16.3° (+ 20%, p = 0.005), after discectomy and insertion of interbody cage to 18.0º (+ 9%, p = 0.012), after resection of the lamina and the processes spinosus to 19.8° (+ 10%, p = 0.017), and after resection of the anterior longitudinal ligament to 25.4° (+ 22%, p = 0.005)., Conclusions: Each step contributed statistically significant to restoration of segmental lordosis with bilateral facetectomy contributing the most in terms of percentage., Level of Evidence: IV., (© 2022. The Author(s).)

Objectives: To investigate the feasibility of the endoscopic approach vs. microscopic approach during stapes surgery, focusing on the visualization of the important anatomical structures of the middle ear, the volume of the resected scutum and chorda tympani (CT) injury., Methods: Fresh frozen human cadaveric heads underwent two stapes surgeries using an operating microscope on one ear and an endoscope on the other ear. The surgeon documented the visualization of critical landmarks, as well as exposure and injury of the CT. The volume of resected scutum was evaluated using cone beam computed tomography scanning and three-dimensional imaging., Results: We performed endoscopic stapes surgery in 10 ears and microscopic stapes surgery in 11 ears. A stapes prosthesis was placed in all ears. The volume of bony scutum resection was significantly lower in the endoscopic group (median = 2.20 mm 3 , IQR = 4.17) than in the microscopic group (median 13.25 mm 3 , IQR = 8.71). No scutum was removed in two endoscopic ears, while scutum was removed in all microscopic ears. The endoscopic and microscopic group had similar CT injury., Conclusions: This study showed that the endoscopic stapes surgery procedure is feasible and might be less invasive than microscopic stapes surgery. Future clinical prospective and functional studies will be needed to support our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Blijleven, Willemsen, Bleys, Stokroos, Wegner and Thomeer.)

Nerve injury of the saphenous nerve or infrapatellar branch seems to be a frequent complication following knee surgery or trauma. Denervation results vary, and in some cases, no pain relief is achieved. This might be due to anatomic variation. The purpose of this anatomical study is to identify the variation in the course of the infrapatellar branch and saphenous nerve. We dissected 18 cadavers from adult donors. Medial to the knee, the saphenous nerve and infrapatellar branch were identified and followed proximally to the point where the infrapatellar branch branched from the saphenous nerve. The location where the infrapatellar branch came off from the saphenous nerve relative to the knee joint and where it passed the knee joint were measured. A total of 23 infrapatellar branches were found. We identified 10 branches between 0-10 cm proximal to the knee joint, 3 branches at 10-20 cm, and 9 branches at >20 cm. Between the patella and semitendinosus tendon, the knee joint was crossed by 5 branches in the anterior, 15 in the middle, and 2 in the posterior one-third. The origin of the infrapatellar branch and the location at which it passes the knee are highly variable. This, in addition to people having multiple branches, might explain why denervation is frequently unsuccessful. Based on the anatomical findings, we propose a more proximal diagnostic nerve block to help differentiate between a distal-middle or proximal origin of the infrapatellar branch. Appropriate placement of the nerve block might help identify people who benefit from denervation., Competing Interests: No author has any form of conflict of interest., (© 2022 The Authors.)

Hypothesis: To develop and validate the optimal design and evaluate accuracy of individualized 3D- printed surgical guides for cochlear implantation., Background: Positioning and fixation of the cochlear implant (CI) are commonly performed free hand. Applications of 3-dimensional (3D) technology now allow us to make patient specific, bone supported surgical guides, to aid CI surgeons with precise placement and drilling out the bony well which accommodates the receiver/stimulator device of the CI., Methods: Cone beam CT (CBCT) scans were acquired from temporal bones in 9 cadaveric heads (18 ears), followed by virtual planning of the CI position. Surgical, bone-supported drilling guides were designed to conduct a minimally invasive procedure and were 3D-printed. Fixation screws were used to keep the guide in place in predetermined bone areas. Specimens were implanted with 3 different CI models. After implantation, CBCT scans of the implanted specimens were performed. Accuracy of CI placement was assessed by comparing the 3D models of the planned and implanted CI's by calculating the translational and rotational deviations., Results: Median translational deviations of placement in the X- and Y-axis were within the predetermined clinically relevant deviation range (< 3 mm per axis); median translational deviation in the Z-axis was 3.41 mm. Median rotational deviations of placement for X-, Y- and Z-rotation were 5.50°, 4.58° and 3.71°, respectively., Conclusion: This study resulted in the first 3D-printed, patient- and CI- model specific surgical guide for positioning during cochlear implantation. The next step for the development and evaluation of this surgical guide will be to evaluate the method in clinical practice., Competing Interests: The authors have declared that no competing interests exist.

Background: In LE (Lateral Epicondylitis) otherwise known as Tennis Elbow, the Extensor Carpi Radialis Brevis (ECRB) tendon is most commonly involved. In the majority of studies, injections are performed with a lack of standardization. The Instant Tennis Elbow Cure (ITEC) device has been developed to perform reproducible and standardized perforations by multiple needles. The goal of this pilot study was to estimate the accuracy of this ITEC device by means of a cadaveric study and to assess the clinical safety of this procedure., Methods: Ten cadaveric arms were injected using the ITEC device. The location and depth of the ECRB tendon was measured by ultrasound imaging. The accuracy of the infiltration was assessed by locating the injected dye through dissection and arthrotomy of the cadaveric elbow. A prospective clinical pilot study was conducted to assess the safety of the ITEC device in treating patients with chronic LE. An optional infiltration with an injection fluid was carried out?? Primary outcome measures were side effects and complications of the ITEC device occurring within a follow up period of 8 weeks after treatment., Results: In all cadaveric elbows the injection fluid ( in this case an injection fluid) was located at the ECRB tendon. In one cadaver, a minimal amount of dye was found intra-articular and in 3 cadavers a small quantity was located in the surrounding tissue of the ECRB tendon. 122 patients with LE were treated with the ITEC device. No adverse effects or complications were reported at 8-week follow up., Conclusion: Treatment of LE using the ITEC device appears accurate and safe. It may improve future research since it is reproducible and it can be performed in a standardized way.

We present the first three-dimensional (3D) concordance maps of cyto- and fiber architecture of the human brain, combining histology, immunohistochemistry, and 7-T quantitative magnetic resonance imaging (MRI), in two individual specimens. These 3D maps each integrate data from approximately 800 microscopy sections per brain, showing neuronal and glial cell bodies, nerve fibers, and interneuronal populations, as well as ultrahigh-field quantitative MRI, all coaligned at the 200-μm scale to the stacked blockface images obtained during sectioning. These unprecedented 3D multimodal datasets are shared without any restrictions and provide a unique resource for the joint study of cell and fiber architecture of the brain, detailed anatomical atlasing, or modeling of the microscopic underpinnings of MRI contrasts.

Calcifications are common in the tunica intima and tunica media of leg arteries. There is growing interest in medial arterial calcifications, as they may be modifiable with treatment. We aimed to investigate radiography and computed tomography (CT) for the detection and characterization of both types of arterial calcification in leg arteries in relation to histology. In a postmortem study we therefore investigated 24 popliteal and 24 tibial arteries. The reference standard was presence of arterial calcification and the dominance of intimal or medial calcification on histology. Radiographs and CT scans were scored for presence of calcification and for dominant intimal or medial pattern based on prespecified criteria (annularity, thickness, continuity). Both radiography and CT detected 87% of histologically proven calcifications but missed mild calcifications in 13%. When only the arteries with detected calcifications were included, a moderate agreement was observed on intimal/medial location of calcifications between histology and radiography (correct in 19/24 arteries (79%); Kappa 0.58) or CT (correct in 33/46 arterial segments (72%); Kappa 0.48). With both modalities there was a slight tendency to classify intimal calcifications as being located in the media and to miss media calcification. Our study demonstrates the potential and limitations of both radiography and CT to detect and classify arterial calcifications in leg arteries.

Objectives: The aim of this study was to investigate the interscanner and interscoring platform variability of calcium quantification in peripheral arteries of the lower extremities., Materials and Methods: Twenty human fresh-frozen legs were scanned using 3 different computed tomography (CT) scanners. The radiation dose (CTDIvol) was kept similar for all scanners. The calcium scores (Agatston and volume scores) were quantified using 4 semiautomatic scoring platforms. Comparative analysis of the calcium scores between scanners and scoring platforms was performed by using the Friedman test; post hoc analysis was performed by using the Wilcoxon signed rank test with Bonferroni correction., Results: Sixteen legs had calcifications and were used for data analysis. Agatston and volume scores ranged from 12.1 to 6580 Agatston units and 18.2 to 5579 mm3. Calcium scores differed significantly between Philips IQon and Philips Brilliance 64 (Agatston: 19.5% [P = 0.001]; volume: 14.5% [P = 0.001]) and Siemens Somatom Force (Agatston: 18.1% [P = 0.001]; volume: 17.5% [P = 0.001]). The difference between Brilliance 64 and Somatom Force was smaller (Agatston: 5.6% [P = 0.778]; volume: 7.7% [P = 0.003]). With respect to the interscoring platform variability, OsiriX produced significantly different Agatston scores compared with the other 3 scoring platforms (OsiriX vs IntelliSpace: 14.8% [P = 0.001] vs Syngo CaScore: 13.9% [P = 0.001] vs iX viewer: 13.2% [P < 0.001]). For the volume score, the differences between all scoring platforms were small ranging from 2.9% to 4.0%. Post hoc analysis showed a significant difference between OsiriX and IntelliSpace (3.8% [P = 0.001])., Conclusions: The use of different CT scanners resulted in notably different Agatston and volume scores, whereas the use of different scoring platforms resulted in limited variability especially for the volume score. In conclusion, the variability in calcium quantification was most evident between different CT scanners and for the Agatston score., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Decreased smile dynamics is reported as an unwanted side effect after Le Fort I osteotomies. It is assumed that this negative sequela might be caused by postoperative changes in the anatomy of peri-oral mimic muscles. Due to a lack of specific anatomical knowledge, the exact mechanism is not yet clarified. This makes prevention of the undesired changes in smile dynamics difficult. The first aim of this study is to increase basic anatomical and radiological MRI knowledge of the peri-oral mimic muscles. The second aim is to investigate if 7 Tesla MRI scans are better suited to identify these muscles than 3 Tesla MRI scans., Methods: Eleven peri-oral mimic muscles were chosen as subjects of the present study. Three and 7 Tesla MRI scans of a cadaver head were made. The same head was cut in axial slices using a cryomacrotome. Every second slice was digitally photographed. A three-dimensional model was created utilizing EMAC software, which served as gold standard for the identification and comparison of the chosen peri-oral mimic muscles on both MRI scans., Results: All predetermined peri-oral mimic muscles could be identified in the cadaver head, and a detailed radiological atlas was created. The ease of identification and separation of the peri-oral mimic muscles was significantly higher on the 7 Tesla MRI than on the 3 Tesla MRI scan ( P < 0.001)., Conclusion: A 7 Tesla MRI scanner offers great improvement in the identification of peri-oral mimic muscles compared with a 3 Tesla scanner., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The cranial pole of the mouse spleen is considered to be parasympathetically innervated by a macroscopic observable nerve referred to as the apical splenic nerve (ASN). Electrical stimulation of the ASN resulted in increased levels of splenic acetylcholine, decreased lipopolysaccharide-induced levels of systemic tumor necrosis factor alpha and mitigated clinical symptoms in a mouse model of rheumatoid arthritis. If such a discrete ASN would be present in humans, this structure is of interest as it might represent a relatively easily accessible electrical stimulation target to treat immune-mediated inflammatory diseases. So far, it is unknown if a human ASN equivalent exists. This study aimed to provide a detailed description of the location and course of the ASN in mice. Subsequently, this information was used for a guided exploration of an equivalent structure in humans. Microscopic techniques were applied to confirm nerve identity and compare ASN composition. Six mice and six human cadavers were used to study and compare the ASN, both macro- and microscopically. Macroscopic morphological characteristics of the ASN in both mice and humans were described and photographs were taken. ASN samples were resected, embedded in paraffin, cut in 5 μm thin sections where after adjacent sections were stained with a general, sympathetic and parasympathetic nerve marker, respectively. Neural identity and nerve fiber composition was then evaluated microscopically. Macroscopically, the ASN could be clearly identified in all mice and was running in the phrenicosplenic ligament connecting the diaphragm and apical pole of the spleen. If a phrenicosplenic ligament was present in humans, a similar configuration of potential neural structures was observed. Since the gastrosplenic ligament was a continuation of the phrenicosplenic ligament, this ligament was explored as well and contained white, potential discrete nerve-like structures as well which could represent an ANS equivalent. Microscopic evaluation of the ASN in mice and human showed that this structure did not represent a nerve, but most likely connective tissue strains. White nerve-like structures, which could represent the ASN, were macroscopically observed in the phrenicosplenic ligament in both mice and human and in the gastrosplenic ligament in humans. The microscopic investigation did not confirm their neural identity and therefore, this study disclaims the existence of a parasympathetic ASN in both mice and human., (© 2021 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Background: The thoracic lymphadenectomy during an esophagectomy for esophageal cancer includes resection of the thoracic duct (TD) compartment containing the TD lymph nodes (TDLNs). The role of TD compartment resection is still a topic of debate since metastatic TDLNs have only been demonstrated in squamous cell carcinomas in Eastern esophageal cancer patients. Therefore, the aim of this study was to assess the presence and metastatic involvement of TDLNs in a Western population, in which adenocarcinoma is the predominant type of esophageal cancer., Methods: From July 2017 to May 2020, all consecutive patients undergoing an open or robot-assisted transthoracic esophagectomy with concurrent lymphadenectomy and resection of the TD compartment in the University Medical Center Utrecht in Utrecht, the Netherlands, and the Città della Salute e della Scienza University Hospital in Turin, Italy, were included. The TD compartment was resected en bloc and was separated in the operation room by the operating surgeon after which it was macroscopically and microscopically assessed for (metastatic) TDLNs by the pathologist., Results: A total of 117 patients with an adenocarcinoma (73%) or squamous cell carcinoma (27%) of the esophagus were included. In 61 (52%) patients, TDLNs were found, containing metastasis in 9 (15%) patients. No major complications related to TD compartment resection were observed., Conclusions: This study demonstrates the presence of metastatic TDLNs in adenocarcinomas of the esophagus. This result provides a valid argument to routinely extend the thoracic lymphadenectomy with resection of the TD compartment during an esophagectomy for esophageal cancer., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

To investigate to what extent the use of a three-dimensional (3D) anatomy computer application can improve the acquisition of anatomical knowledge compared with anatomical atlases, junior and advanced medical students participated in an experiment. Participants were asked to answer anatomical questions with the use of a 3D anatomy application (developed at the University Medical Center in Utrecht, the Netherlands) or anatomy atlases. Every student had to complete two assignments, either with an atlas or with the 3D anatomy application. One assignment consisted of 20 questions about the anatomy of the hand, the other one had 20 questions about the anatomy of the foot. The scores on the assignments and time to complete the assignments were registered and investigated. A total of 76 students participated. Students scored significantly higher and were significantly faster when they used the 3D anatomy application. Junior medical students were significantly faster than advanced medical students and particularly, advanced students who worked with an atlas needed most time. These results suggest that the 3D anatomy application is more effective as a studying tool, when compared to the use of paper atlases, for both junior and advanced medical students. The difference in time could indicate an influence of the increased number of mental steps it takes to convert two-dimensional atlas images to a 3D mental representation compared to using the 3D anatomy application, although practical issues explaining this cannot be ruled out. Future studies should establish whether the application leads to better learning/retention and to more time-efficient studying., (© 2021 American Association for Anatomy.)

Purpose: Computed tomography (CT) might be a good diagnostic test to accurately quantify calcium in vascular beds but there are multiple factors influencing the quantification. The aim of this study was to investigate the influence of different computed tomography protocol settings in the quantification of calcium in the lower extremities using modified Agatston and volume scores., Methods: Fresh-frozen human legs were scanned at different tube current protocols and reconstructed at different slice thickness. Two different iterative reconstruction protocols for conventional CT images were compared. Calcium was manually scored using modified Agatston and volume scores. Outcomes were statistically analyzed using Wilcoxon signed-rank tests and mean absolute and relative differences were plotted in Bland-Altman plots., Results: Of the 20 legs, 16 had CT detectable calcifications. Differences between thick and thin slice reconstruction protocols were 129 Agatston units and 125% for Agatston and 78.4 mm 3 and 57.8% for volume (all p ≤ 0.001). No significant differences were found between low and high tube current protocols. Differences between iDose 4 and IMR reconstruction protocols for modified Agatston were 34.2 Agatston units and 17.7% and the volume score 33.5 mm 3 and 21.2% (all p ≤ 0.001)., Conclusions: Slice thickness reconstruction and reconstruction method protocols influenced the modified Agatston and volume scores in leg arteries, but tube current and different observers did not have an effect. This data emphasizes the need for standardized quantification of leg artery calcifications. Possible implications are in the development of a more universal quantification method, independent of the type of scan and vasculature., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Robot-assisted cervical esophagectomy (RACE) enables radical surgery for tumors of the middle and upper esophagus, avoiding a transthoracic approach. However, the cervical access, narrow working space, and complex topographic anatomy make this procedure particularly demanding. Our study offers a stepwise description of appropriate dissection planes and anatomical landmarks to facilitate RACE. Macroscopic dissections were performed on formaldehyde-fixed body donors (three females, three males), according to the surgical steps during RACE. The topographic anatomy and surgically relevant structures related to the cervical access route to the esophagus were described and illustrated, along with the complete mobilization of the cervical and upper thoracic segment. The carotid sheath, intercarotid fascia, and visceral fascia were identified as helpful landmarks, used as optimal dissection planes to approach the cervical esophagus and preserve the structures at risk (trachea, recurrent laryngeal nerves, thoracic duct, sympathetic trunk). While ventral dissection involved detachment of the esophagus from the tracheal cartilage and membranous part, the dorsal dissection plane comprised the prevertebral compartment harboring the thoracic duct and right intercosto-bronchial artery. On the left side, the esophagus was attached to the aortic arch by the aorto-esophageal ligament; on the right side, the esophagus was bordered by the azygos vein, right vagus nerve, and cardiac nerves. The stepwise, illustrated topographic anatomy addressed specific surgical demands and perspectives related to the left cervical approach and dissection of the esophagus, providing an anatomical basis to facilitate and safely implement the RACE procedure., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: A commonly seen issue in facial palsy patients is brow ptosis caused by paralysis of the frontalis muscle powered by the frontal branch of the facial nerve. Predominantly, static methods are used for correction. Functional restoration concepts include the transfer of the deep temporal branch of the trigeminal nerve and cross-facial nerve grafts. Both techniques can neurotize the original mimic muscles in early cases or power muscle transplants in late cases. Because axonal capacity is particularly important in cross-facial nerve graft procedures, the authors investigated the microanatomical features of the frontal branch to provide the basis for its potential use and to ease intraoperative donor nerve selection., Methods: Nerve biopsy specimens from 106 fresh-frozen cadaver facial halves were obtained. Histologic processing and digitalization were followed by nerve morphometric analysis and semiautomated axon quantification., Results: The frontal branch showed a median of three fascicles (n = 100; range, one to nine fascicles). A mean axonal capacity of 1191 ± 668 axons (range, 186 to 3539 axons; n = 88) and an average cross-sectional diameter of 1.01 ± 0.26 mm (range, 0.43 to 1.74 mm; n = 67) were noted. In the linear regression model, diameter and axonal capacity demonstrated a positive relation (n = 57; r2 = 0.32; p < 0.001). Based on that equation, a nerve measuring 1 mm is expected to carry 1339 axons., Conclusion: The authors' analysis on the microanatomy of the frontal branch could promote clinical use of cross-facial nerve graft procedures in frontalis muscle neurotization and free muscle transplantations., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Introduction: The cholinergic anti-inflammatory pathway (CAIP) has been proposed as an efferent neural pathway dampening the systemic inflammatory response via the spleen. The CAIP activates the splenic neural plexus and a subsequent series of intrasplenic events, which at least require a close association between sympathetic nerves and T cells. Knowledge on this pathway has mostly been derived from rodent studies and only scarce information is available on the innervation of the human spleen. This study aimed to investigate the sympathetic innervation of different structures of the human spleen, the topographical association of nerves with T cells and age-related variations in nerve distribution. Materials and Methods: Spleen samples were retrieved from a diagnostic archive and were allocated to three age groups; neonates, 10-25 and 25-70 years of age. Sympathetic nerves and T cells were identified by immunohistochemistry for tyrosine hydroxylase (TH) and the membrane marker CD3, respectively. The overall presence of sympathetic nerves and T cells was semi-automatically quantified and expressed as total area percentage. A predefined scoring system was used to analyze the distribution of nerves within different splenic structures. Results: Sympathetic nerves were observed in all spleens and their number appeared to slightly increase from birth to adulthood and to decrease afterward. Irrespective to age, more than halve of the periarteriolar lymphatic sheaths (PALSs) contained sympathetic nerves in close association with T cells. Furthermore, discrete sympathetic nerves were observed in the capsule, trabeculae and red pulp and comparable to the total amount of sympathetic nerves, showed a tendency to decrease with age. No correlation was found between the number of T cells and sympathetic nerves. Conclusion: The presence of discrete sympathetic nerves in the splenic parenchyma, capsule and trabecular of human spleens could suggest a role in functions other than vasoregulation. In the PALS, sympathetic nerves were observed to be in proximity to T cells and is suggestive for the existence of the CAIP in humans. Since sympathetic nerve distribution shows interspecies and age-related variation, and our general understanding of the relative and spatial contribution of splenic innervation in immune regulation is incomplete, it remains difficult to estimate the anti-inflammatory potential of targeting splenic nerves in patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cleypool, Brinkman, Mackaaij, Nikkels, Nolte, Luyer, de Jonge and Bleys.)

Introduction: Although arteries of the leg have been studied in extensively diseased amputation specimens, little is known about the composition of vascular lesions present in the general population. The aim of this study was to describe the natural development of adaptive intimal thickening, atherosclerotic lesion development and vascular calcification in the leg of a general elderly population., Materials and Methods: Two hundred and seventy postmortem samples from the popliteal and posterior tibial arteries of 14 elderly cadavers were studied histologically., Results: Atherosclerotic lesions were more frequently observed in the popliteal (60%) than in the posterior tibial artery (34%; p < .0005). These atherosclerotic plaques were most often nonatheromatous (80% and 83% for popliteal and posterior tibial plaques, respectively). The atheroma's that were present were small (most <25% of plaque area). Atherosclerotic plaque calcification was observed more often in the popliteal (39%) than in the posterior tibial samples (17%; p < .0005). Medial arterial calcification was observed more often in the posterior tibial (62%) than in the popliteal samples (46%; p = .008). Plaque calcification and medial arterial calcification were not associated with lumen stenosis., Conclusions: In the leg of elderly cadavers, the presence of atherosclerotic plaque and intimal calcification decreases from the proximal popliteal artery to the more distal posterior tibial artery and most atherosclerotic lesions are of the fibrous nonatheromatous type. In contrast, the presence and severity of medial calcification increases from proximal to distal., (© 2020 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists.)

Various lymph node functions are regulated by the sympathetic nervous system as shown in rodent studies. If human lymph nodes show a comparable neural regulation, their afferent nerves could represent a potential therapeutic target to treat, for example, infectious or autoimmune disease. Little information is available on human lymph node innervation and the aim of this study is to establish a comprehensive and accurate representation of the presence and location of sympathetic nerves in human lymph nodes. Since previous studies mention sympathetic paravascular nerves to occasionally extent into T cell-rich regions, the relation of these nerves with T cells was studied as well. A total number of 15 inguinal lymph nodes were resected from six donated human cadavers. Lymph node sections were stained with HE and a double T/B cell staining for evaluation of their morphology and to screen for general pathologies. A triple stain was used to identify blood vessels, sympathetic nerves and T cells, and, to study the presence and location of sympathetic nerves and their relation to T cells. To evaluate whether the observed nerves were en route to other structures or were involved in local processes, adjacent slides were stained with a marker for varicosities (synaptophysin), which presence is suggestive for synaptic activity. All lymph nodes contained sympathetic nerves, both as paravascular and discrete structures. In 15/15 lymph nodes, nerves were observed in their capsule, medulla and hilum, whereas only 13/15 lymph nodes contained nerves in their cortex. The amount of sympathetic nerves varied between compartments and between and within individuals. In general, if a lymph node contained more paravascular nerves in a specific compartment, more discrete nerves were observed as well. Occasionally, discrete nerves were observed in relation to T cells in lymphoid tissues of the cortex and medulla. Furthermore, discrete nerves were frequently present in the capsule and hilum. The presence of varicosities in a portion of these nerves, independently to their compartment, suggested a local regulatory function for these nerves. Human lymph nodes contain sympathetic nerves in their capsule, trabeculae, cortex, medulla and hilum, both as paravascular or as discrete structures. Discrete nerves were observed in relation to T cells and non-T cell-rich areas such as the hilar and capsular connective tissue. The presence of discrete structures suggests neural regulation of structures other than blood vessels, which was further supported by the presence of varicosities in a portion of these nerves. These observations are of relevance in further understanding neural regulation of lymph node immune responses and in the development of neuromodulatory immune therapies., (© 2021 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Recent insights suggest that the osteochondral interface plays a central role in maintaining healthy articulating joints. Uncovering the underlying transport mechanisms is key to the understanding of the cross-talk between articular cartilage and subchondral bone. Here, we describe the mechanisms that facilitate transport at the osteochondral interface. Using scanning electron microscopy (SEM), we found a continuous transition of mineralization architecture from the non-calcified cartilage towards the calcified cartilage. This refurbishes the classical picture of the so-called tidemark; a well-defined discontinuity at the osteochondral interface. Using focused-ion-beam SEM (FIB-SEM) on one osteochondral plug derived from a human cadaveric knee, we elucidated that the pore structure gradually varies from the calcified cartilage towards the subchondral bone plate. We identified nano-pores with radius of 10.71 ± 6.45 nm in calcified cartilage to 39.1 ± 26.17 nm in the subchondral bone plate. The extracted pore sizes were used to construct 3D pore-scale numerical models to explore the effect of pore sizes and connectivity among different pores. Results indicated that connectivity of nano-pores in calcified cartilage is highly compromised compared to the subchondral bone plate. Flow simulations showed a permeability decrease by about 2000-fold and solute transport simulations using a tracer (iodixanol, 1.5 kDa with a free diffusivity of 2.5 × 10 -10 m 2 /s) showed diffusivity decrease by a factor of 1.5. Taken together, architecture of the nano-pores and the complex mineralization pattern in the osteochondral interface considerably impacts the cross-talk between cartilage and bone., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Injection therapy around the distal biceps tendon insertion is challenging. This therapy may be indicated in patients with a partial distal biceps tendon tear, bicipitoradial bursitis and tendinopathy. The primary goal of this study was to determine the accuracy of manually performed injections without ultrasound guidance around the biceps tendon., Methods: Seven upper limb specialists, two general orthopedic specialists, and three orthopedic surgical residents manually injected a cadaver elbow with acrylic dye using an anterior and a lateral infiltration approach. After infiltration the cadaveric elbows were dissected to determine the location of the acrylic dye., Results: In total, 79% of the injections were localized near the biceps tendon. Of these injections, 20% were localized on the radius near the bicipitoradial bursa. In total, 53% of the performed infiltrations were injected by anterior and 47% by lateral approaches. Of the injections near the distal biceps (79%), 47% were injected by an anterior and 53% by a lateral approach. Of the injections on the radius (20%), 33% were injected by anterior and 67% by lateral approach. Of the inaccurate injections (21%), 75% were injected anterior and 25% lateral., Conclusion: Manual infiltration without ultrasound guidance for distal biceps pathology lacks accuracy. We therefore recommend ultrasound guidance for more accurate infiltration.

Introduction: The splenic plexus might represent a novel neuroimmunomodulatory therapeutic target as electrical stimulation of this tissue has been shown to have beneficial anti-inflammatory effects. Tortuous splenic artery segments (splenic artery loops), including their surrounding nerve plexus, have been evaluated as potential stimulation sites in humans. At present, however, our understanding of these loops and their surrounding nerve plexus is incomplete. This study aims to characterize the dimensions of these loops and their surrounding nerve tissue., Materials and Methods: Six formaldehyde fixed human cadavers were dissected and qualitative and quantitative macro- and microscopic data on splenic artery loops and their surrounding nerve plexus were collected., Results: One or multiple loops were observed in 83% of the studied specimens. These loops, including their surrounding nerve plexus could be easily dissected free circumferentially thereby providing sufficient space for further surgical intervention. The splenic plexus surrounding the loops contained a significant amount of nerves that contained predominantly sympathetic fibers., Conclusion: The results of this study support that splenic artery loops could represent suitable electrical splenic plexus stimulation sites in humans. Dimensions with respect to loop height and width, provide sufficient space for introduction of surgical instruments and electrode implantation, and, the dissected neurovascular bundles contain a substantial amount of sympathetic nerve tissue. This knowledge may contribute to further development of surgical techniques and neuroelectrode interface design., (© 2020 The Authors. Clinical Anatomy published by Wiley Periodicals LLC. on behalf of American Association of Clinical Anatomists.)

Pathology in the bicipital groove can be a source of anterior shoulder pain. Many studies have compared treatment techniques for the long head biceps tendon (LHBT) without showing any clinically significant differences. As the LHBT is closely related to the bicipital groove, anatomical aspects of this groove could also be implicated in surgical outcomes. The aim of this review is to contribute to developing the optimal surgical treatment of LHBT pathology based on clinically relevant aspects of the bicipital groove. Medline/PubMed was systematically searched using key words "bicipital" and "groove" and combinations of their synonyms. Studies reporting on evolution, embryonic development, morphometry, vascularization, innervation, and surgical treatment of the LHBT and the bicipital groove were included. The length of the bicipital groove reported in the included studies ranged from 81.00 mm to 87.33 mm, width from 7.74 mm to 11.60 mm, and depth from 3.70 mm to 6.00 mm. The anatomy of the bicipital groove shows a bottleneck narrowing approximately two-thirds from superior. The transverse humeral ligament can constrain the bicipital groove and could be involved in anterior shoulder pain. When either LHBT tenotomy or tenodesis is performed, routinely releasing the transverse ligament could decrease postoperative anterior shoulder pain, which has frequently been reported in the literature. To avoid the bottle neck narrowing, a location below the bicipital groove may be preferred for biceps tenodesis over a more proximal tenodesis site. Level of evidence: IV., (© 2020 Wiley Periodicals LLC.)

Objective: To describe the feasibility of a fresh frozen human cadaver model for research and training of endovascular image guided procedures in the aorta and lower extremity., Methods: The cadaver model was constructed in fresh frozen human cadaver torsos and lower extremities. Endovascular access was acquired by inserting a sheath in the femoral artery. The arterial segment of the specimen was restricted by ligation of collateral arteries and, in the torsos, clamping of the contralateral femoral artery and balloon occlusion of the supratruncal aorta. Tap water was administered through the sheath to create sufficient intraluminal pressure to manipulate devices and acquire digital subtraction angiography (DSA). Endovascular cannulation tasks of the visceral arteries (torso) or the peripheral arteries (lower extremities) were performed to assess the vascular patency of the model. Feasibility of this model is based on our institute's experiences throughout the use of six fresh frozen human cadaver torsos and 22 lower extremities., Results: Endovascular simulation in the aortic and peripheral vasculature was achieved using this human cadaver model. Acquisition of DSA images was feasible in both the torsos and the lower extremities. Approximately 84 of the 90 target vessels (93.3%) were patent, the remaining six vessels showed signs of calcified steno-occlusive disease., Conclusions: Fresh frozen human cadavers provide a feasible simulation model for aortic and peripheral endovascular interventions, and can potentially reduce the need for animal experimentation. This model is suitable for the evaluation of new endovascular devices and techniques or to master endovascular skills., Competing Interests: The authors have declared that no competing interests exist.

Background: Omental milky spots (OMSs) are the primary lymphoid structures of the greater omentum. However, the presence of lymph nodes (LNs) has occasionally been mentioned as well. Understanding which lymphoid structures are present is of significance, especially in gastric tumor metastasis; tumor deposits in omental LNs suggest local lymphatic spread, whereas tumor deposits in OMSs suggest peritoneal spread and hence extensive disease. Since LNs and OMSs share morphological characteristics and OMSs might be wrongly identified as LNs, reliable hallmarks facilitating easy discrimination are needed., Materials and Method: A series of microscopic morphological hallmarks unique to LNs were selected as potential candidates and were assessed for their discriminative capacity: 1) capsule, 2) trabeculae, 3) subcapsular sinus, 4) afferent lymphatic vessels, 5) distinct B- and T cell regions, and 6) a layered organization with, from the outside in a capsule, cortex, paracortex, and medulla. These hallmarks were visualized by multiple staining techniques., Results: Hallmarks 1, 2 5 and 6 were shown to be the most efficient as these were consistent and discriminative. They were best visualized by Picrosirius red, smooth muscle actin and a B-cell / T-cell double staining., Conclusion: The presence of a capsule, trabeculae, distinct B- and T-cell regions and a layered organization represent consistent and reliable morphological features which allow to easily distinguish LNs from OMSs, especially when applied in combination.

Post mortem magnetic resonance imaging (MRI) studies on the human brain are of great interest for the validation of in vivo MRI. It facilitates a link between functional and anatomical information available from MRI in vivo and neuroanatomical knowledge available from histology/immunocytochemistry. However, linking in vivo and post mortem MRI to microscopy techniques poses substantial challenges. Fixation artifacts and tissue deformation of extracted brains, as well as co registration of 2D histology to 3D MRI volumes complicate direct comparison between modalities. Moreover, post mortem brain tissue does not have the same physical properties as in vivo tissue, and therefore MRI approaches need to be adjusted accordingly. Here, we present a pipeline in which whole-brain human post mortem in situ MRI is combined with subsequent tissue processing of the whole human brain, providing a 3-dimensional reconstruction via blockface imaging. To this end, we adapted tissue processing procedures to allow both post mortem MRI and subsequent histological and immunocytochemical processing. For MRI, tissue was packed in a susceptibility matched solution, tailored to fit the dimensions of the MRI coil. Additionally, MRI sequence parameters were adjusted to accommodate T1 and T2 ∗ shortening, and scan time was extended, thereby benefiting the signal-to-noise-ratio that can be achieved using extensive averaging without motion artifacts. After MRI, the brain was extracted from the skull and subsequently cut while performing optimized blockface imaging, thereby allowing three-dimensional reconstructions. Tissues were processed for Nissl and silver staining, and co-registered with the blockface images. The combination of these techniques allows direct comparisons across modalities., (Copyright © 2020 Alkemade, Pine, Kirilina, Keuken, Mulder, Balesar, Groot, Bleys, Trampel, Weiskopf, Herrler, Möller, Bazin and Forstmann.)

Background: Conjoined twinning is a rare congenital malformation with an incidence of about 1.5 per 100,000 births. Because no consensus has been reached regarding the dysmorphology, thorough descriptions of conjoined twins as part of teratological collections can be useful to increase knowledge of this congenital malformation. In this case report, we describe a parapagus dicephalus twin from the collection of the Department of Anatomy of the University Medical Center Utrecht in the Netherlands. External anatomical characteristics were assessed through a detailed macroscopic examination and internal characteristics by means of whole-body computed tomography and magnetic resonance imaging (3 Tesla)., Case Presentation: Macroscopic examination showed a Caucasian male parapagus dicephalus tripus tribrachius conjoined twin a type of conjoined twinning in which there are two heads side by side, one rump, and three upper and three lower limbs. In addition, anencephaly was observed in the left twin. Radiological imaging showed a normal central nervous system in the right twin and absence of the calvaria, cerebrum, diencephalon, and mesencephalon in the left twin. There was clear duplication of the vertebral column, rib cage, respiratory system, and gastrointestinal system at least up to and including the first part of the duodenum. The heart consisted of a monoatrium with two separate ventricles. There was a fused liver with a single gallbladder, a single spleen, three kidneys, two bladders, and duplication of the penis. The third upper and lower extremities were articulating with a fused glenoid and acetabulum, respectively. The third foot showed both polydactyly and syndactyly of the toes., Conclusion: This case report describes a unique case of a male dicephalus parapagus tripus tribrachus conjoined twin discordant for anencephaly. Radiological imaging proved to be an adequate noninvasive method to provide insights into the internal (dys)morphology of this specific specimen, improving its scientific and educational value. This approach could be generally applied to other teratological specimens, thereby strengthening arguments regarding pathogenetic hypotheses, which may lead to new or improved insights into both normal and abnormal embryonic development.

Background: Knowledge of tip supporting structures is crucial for successful rhinoplastic surgery. The aim of this study was to provide detailed anatomical and histological descriptions of the tip supporting structures., Methods: Serial coronal sections of the entire external noses from seven cadavers were studied after staining by Mallory-Cason and Verhoeff-Van Gieson procedures., Results and Conclusions: We found no histological evidence of ligaments between the cartilaginous- and bony parts of the nasal skeleton, and between the skin and the nasal skeleton. Instead, we found a perichondrial-periosteal lining within the soft tissue envelope. The main tip supporting and shaping structures are: septal and lobular cartilages, premaxillae, and the soft tissue envelope including the periosteal-perichondrial envelope/membrane. These findings may have clinical relevance in functional and aesthetic rhinoplasties.

Purpose: Ulnar nerve injury is the most common neurologic complication of elbow arthroscopy. The purpose of this cadaveric study was to quantify the ability of surgeons to locate the ulnar nerve behind the posteromedial capsule during elbow arthroscopy using sole arthroscopic vision., Methods: Twenty-one surgeons were asked to pin the ulnar nerve at the medial gutter and the posteromedial compartment using arthroscopic visualization of the medial capsule only. Pinning of the ulnar nerve was performed from extra-articular. Then, the cadaveric specimens were dissected and the shortest distances between the pins and ulnar nerve measured., Results: Median pin-to-nerve distances at the medial gutter and posteromedial compartment were 0 mm (interquartile range [IQR], 0-3 mm) and 2 mm (IQR, 0-6 mm), respectively. The ulnar nerve was pinned by 11/21 surgeons (52%) at the medial gutter, and 7/21 surgeons (33%) at the posteromedial compartment. Three of 21 surgeons (14%) pinned the ulnar nerve at both the medial gutter and the posteromedial compartment. Surgeon's experience and operation volume did not affect these outcomes ( P > .05)., Conclusions: Surgeons' ability to locate the ulnar nerve behind the posteromedial capsule using sole arthroscopic visualization, without external palpation, is poor. We recommend to proceed carefully when performing arthroscopic procedures in the posteromedial elbow, and identify and mobilize the ulnar nerve prior to any posteromedial capsular procedures., (© 2020 The Authors.)

Background: Extra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions., Methods: All patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012-December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates., Results: From 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up., Conclusions: The majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Traditional carotid endarterectomy is considered to be the standard technique for prevention of a new stroke in patients with a symptomatic carotid stenosis. Use of patch angioplasty to restore the arterial wall after longitudinal endarterectomy is, to date, not unequivocally proven to be superior to eversion technique. A systematic review is needed for evaluation of benefits and harms of the eversion technique versus the traditional endarterectomy with patch angioplasty in patients with symptomatic carotid stenosis., Methods and Outcomes: The review will be conducted according to this protocol following the recommendations of the 'Cochrane Handbook for Systematic Reviews' and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Randomised clinical trials comparing eversion technique versus endarterectomy with patch angioplasty in patients with a symptomatic stenosis of the internal carotid artery will be included. Primary outcomes are all-cause mortality rate, health-related quality of life and serious adverse events. Secondary outcomes are 30-day stroke and mortality rate, symptomatic arterial restenosis or occlusion and non-serious adverse events. The databases Cochrane Central Register of Controlled Trials, PubMed/MEDLINE and EMBASE will be searched (November 2019). We will primarily base our conclusions on meta-analyses of trials with overall low-risk of bias. We will use trial sequential analysis to assist the evaluation of imprecision in Grading of Recommendations, Assessment, Development and Evaluation. However, if pooled point estimates of all trials are similar to pooled point estimates of trials with overall low risk of bias and there is lack of a statistical significant interaction between estimates from trials with overall high risk of bias and trials with overall low risk of bias we will consider the trial sequential analysis adjusted precision of the estimate achieved in all trials as the result of our meta-analyses., Ethics and Dissemination: The proposed systematic review will collect and analyse data from published studies, therefore, ethical approval is not required. The results of the review will be disseminated by publication in a peer-review journal and submitted for presentation at conferences., Prospero Registration Number: CRD42019119361., Competing Interests: Competing interests: JW is a member of the taskforce at Copenhagen Trial Unit to develop theory and software doing TSA, presently available as freeware at www.ctu.dk/tsa., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Silicon dioxide (silica, SiO 2 , SAS) and titanium dioxide (TiO 2 ) are produced in high volumes and applied in many consumer and food products. As a consequence, there is a potential human exposure and subsequent systemic uptake of these particles. In this study we show the characterization and quantification of both total silicon (Si) and titanium (Ti), and particulate SiO 2 and TiO 2 in postmortem tissue samples from 15 deceased persons. Included tissues are liver, spleen, kidney and the intestinal tissues jejunum and ileum. Low-level analysis was enabled by the use of fully validated sample digestion methods combined with (single particle) inductively coupled plasma high resolution mass spectrometry techniques (spICP-HRMS). The results show a total-Si concentration ranging from <2 to 191 mg Si/kg (median values of 5.8 (liver), 9.5 (spleen), 7.7 (kidney), 6.8 (jejunum), 7.6 (ileum) mg Si/kg) while the particulate SiO 2 ranged from <0.2 to 25 mg Si/kg (median values of 0.4 (liver), 1.0 (spleen), 0.4 (kidney), 0.7 (jejunum, 0.6 (ileum) mg Si/kg), explaining about 10% of the total-Si concentration. Particle sizes ranged from 150 to 850 nm with a mode of 270 nm. For total-Ti the results show concentrations ranging from <0.01 to 2.0 mg Ti/kg (median values of 0.02 (liver), 0.04 (spleen), 0.05 (kidney), 0.13 (jejunum), 0.26 (ileum) mg Ti/kg) while particulate TiO 2 concentrations ranged from 0.01 to 1.8 mg Ti/kg (median values of 0.02 (liver), 0.02 (spleen), 0.03 (kidney), 0.08 (jejunum), 0.25 (ileum) mg Ti/kg). In general, the particulate TiO 2 explained 80% of the total-Ti concentration. This indicates that most Ti in these organ tissues is particulate material. The detected particles comprise primary particles, aggregates and agglomerates, and were in the range of 50-500 nm with a mode in the range of 100-160 nm. About 17% of the detected TiO 2 particles had a size <100 nm. The presence of SiO 2 and TiO 2 particles in liver tissue was confirmed by scanning electron microscopy with energy dispersive X-ray spectrometry.

We developed a time-efficient semi-automated axon quantification method using freeware in human cranial nerve sections stained with paraphenylenediamine (PPD). It was used to analyze a total of 1238 facial and masseteric nerve biopsies. The technique was validated by comparing manual and semi-automated quantification of 129 (10.4%) randomly selected biopsies. The software-based method demonstrated a sensitivity of 94% and a specificity of 87%. Semi-automatic axon counting was significantly faster (p < 0.001) than manual counting. It took 1 hour and 47 minutes for all 129 biopsies (averaging 50 sec per biopsy, 0.04 seconds per axon). The counting process is automatic and does not need to be supervised. Manual counting took 21 hours and 6 minutes in total (average 9 minutes and 49 seconds per biopsy, 0.52 seconds per axon). Our method showed a linear correlation to the manual counts (R = 0.944 Spearman rho). Attempts have been made by several research groups to automate axonal load quantification. These methods often require specific hard- and software and are therefore only accessible to a few specialized laboratories. Our semi-automated axon quantification is precise, reliable and time-sparing using publicly available software and should be useful for an effective axon quantification in various human peripheral nerves.

Omental milky spots (OMSs), small lymphoid structures positioned in the greater omentum, are involved in peritoneal immune homeostasis and the formation of omental metastases. Sympathetic nerve activity is known to regulate immune function in other lymphoid organs (e.g. spleen and lymph nodes) and to create a favourable microenvironment for various tumour types. However, it is still unknown whether OMSs receive sympathetic innervation. Therefore, the aim of this study was to establish whether OMSs of the adult human greater omentum receive sympathetic innervation. A total of 18 OMSs were isolated from five omenta, which were removed from 3% formaldehyde-perfused cadavers (with a median age of 84 years, ranging from 64 to 94). OMSs were embedded in paraffin, cut and stained with a general (PGP9.5) and sympathetic nerve marker (TH and DBH), and evaluated by bright field microscopy. A T-cell, B-cell, and macrophage staining was performed to confirm OMS identity. In 50% of the studied OMSs, sympathetic nerve fibres were observed at multiple levels of the same OMS. Nerve fibres were represented as dots or elongated structures and often observed in relation to small vessels and occasionally as individual structures residing between lymphoid cells. The current study shows that 50% of the investigated OMSs contain sympathetic nerve fibres. These findings may contribute to our understanding of neural regulation of peritoneal immune response and the involvement of OMSs in omental metastases., (© 2019 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)