The Ability to Sustain Facial Expressions.

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.

The legal and ethical framework governing body donation in Europe - 2nd update on current practice.

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.

Eversion technique versus traditional carotid endarterectomy with patch angioplasty: a systematic review with meta-analyses and trial sequential analysis.

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.

A novel anatomical description of the esophagus: the supracarinal mesoesophagus.

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.

The Average Facial Expressions: A Range of Motion Analysis for Different Sex and Age Groups.

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.

The clinical significance of the human vomeronasal organ.

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.

Endoscopic vs. microscopic stapes surgery: An anatomical feasibility study.

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 mm3, IQR = 4.17) than in the microscopic group (median 13.25 mm3, 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.

Are We Facing the End of Gross Anatomy Teaching as We Have Known It for Centuries?

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.

The origin and course of the infrapatellar branch of the saphenous nerve: An anatomical study.

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.

Cochlear implant positioning and fixation using 3D-printed patient specific surgical guides; a cadaveric study.

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.

Multiple Perforations of the ECRB Tendon Using an Innovative Standardized, Reproducible Technique; A Cadaveric Study on Accuracy and Prospective Clinical Safety Assessment Pilot Study. No Adverse Effects in the First 122 Patients with Lateral Epicondylitis.

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.

Radiography and Computed Tomography Detection of Intimal and Medial Calcifications in Leg Arteries in Comparison to Histology.

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.

A unified 3D map of microscopic architecture and MRI of the human brain.

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.

Identification of the Peri-oral Mimic Muscles on Cadaver Slices and 3 and 7 Tesla MRI Scans.

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.

Computed tomography-based calcium scoring in cadaver leg arteries: Influence of dose, reader, and reconstruction algorithm.

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 mm3 and 57.8% for volume (all p ≤ 0.001). No significant differences were found between low and high tube current protocols. Differences between iDose4 and IMR reconstruction protocols for modified Agatston were 34.2 Agatston units and 17.7% and the volume score 33.5 mm3 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.

A comparative anatomical and histological study on the presence of an apical splenic nerve in mice and humans.

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.

Quantification of Calcium in Peripheral Arteries of the Lower Extremities: Comparison of Different CT Scanners and Scoring Platforms.

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.

Support for using a three-dimensional anatomy application over anatomical atlases in a randomized comparison.

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.

The Presence of Metastatic Thoracic Duct Lymph Nodes in Western Esophageal Cancer Patients: A Multinational Observational Study.

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.

Age-Related Variation in Sympathetic Nerve Distribution in the Human Spleen.

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.