Microsurgical central lymphatic reconstruction-the role of thoracic duct lymphovenous anastomoses at different anatomical levels.

Introduction: In recent years advances have been made in the microsurgical treatment of congenital or acquired central lymphatic lesions. While acquired lesions can result from any surgery or trauma of the central lymphatic system, congenital lymphatic lesions can have a variety of manifestations, ranging from singular thoracic duct abnormalities to complex multifocal malformations. Both conditions may cause recurrent chylous effusions and downstream lymphatic congestion depending on the anatomical location of the thoracic duct lesion and are associated with an increased mortality due to the permanent loss of protein and fluid. Methods: We present a case series of eleven patients undergoing central lymphatic reconstruction, consisting of one patient with a cervical iatrogenic thoracic duct lesion and eleven patients with different congenital thoracic duct lesions or thrombotic occlusions. Results: Anastomosis of the thoracic duct and a nearby vein was performed on different anatomical levels depending on the underlying central lymphatic pathology. Cervical (n = 4), thoracic (n = 1) or abdominal access (n = 5) was used for central lymphatic reconstruction with promising results. In 9 patients a postoperative benefit with varying degrees of symptom regression was reported. Conclusion: The presented case series illustrates the current rapid advances in the field of central microsurgical reconstruction of lymphatic lesions alongside the relevant literature.

Evaluation of the Effect of Botulinum Toxin A on the Lymphatic Endothelial Cells.

INTRODUCTION: Botulinum toxin A (BoTA) is a neurotoxin formed by Clostridium botulinum, with a broad medical application spectrum. While the primary effect of BoTA is on the muscles, the effects of BoTA in other systems including the blood vasculature have already been examined, revealing unexpected actions. However, no studies exist to the best of our knowledge regarding the potential effects of BoTA on the lymphatic vascular system, possessing a critical role in health and disease. Isolated human lymphatic endothelial cells (LECs) were cultured in dedicated in vitro culture systems. The analysis including imaging and cell culture approaches as well as molecular biology techniques is performed to examine the LEC alterations occurring upon exposure to different concentrations of BoTA. MATERIALS AND METHODS: Human LECs were cultured and expanded on collagen-coated petri dishes using endothelial basal medium and the commercial product Botox from Allergan as used for all our experiments. Harvested cells were used in various in vitro functional tests to assess the morphologic and functional properties of the BoTA-treated LECs. Gene expression analysis was performed to assess the most important lymphatic system-related genes and pathways. RESULTS: Concentrations of 1, 5 or 10 U of BoTA did not demonstrate a significant effect regarding the proliferation and migration capacity of the LECs versus untreated controls. Interestingly, even the smallest BoTA dose was found to significantly decrease the cord-like-structure formation capacity of the seeded LECs. Gene expression analysis was used to underpin possible molecular alterations, suggesting no significant effect of BoTA in the modification of gene expression versus the starvation medium control. CONCLUSION: LECs appear largely unaffected to BoTA treatment, with an isolated effect on the cord-like-structure formation capacity. Further work needs to assess the effect of BoTA on the smooth-muscle-cell-covered collecting lymphatic vessels and the possible aesthetic implications of such an effect, due to edema formation. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Analysis of different outcome parameters and quality of life after different techniques of free vascularized lymph node transfer.

OBJECTIVE: Vascularized lymph node transfer (VLNT) has become an important surgical technique in the treatment of lymphedema. Considering the different available regions available for flap harvest, we aimed to analyze different donor sites for VLNT with respect to donor-site morbidity, impact on limb volume and patient-reported outcome measurements (PROMs). METHODS: A single-center prospective study on all patients receiving VLNT at the Department of Plastic Surgery and Hand Surgery of the University Hospital Zurich between September 2016 and 2023 was conducted. Lymph nodes were harvested either from the omentum (GE-VLNT), the lateral thoracic wall (LTW) or the superficial inguinal region (SI-VLNT). Volume measurements and PROMs were assessed preoperatively and at different postoperative intervals. RESULTS: Overall, 70 patients with upper limb lymphedema (21%) or lower limb lymphedema (79%) with different lymphedema stages were included. 49 patients received GE-VLNT, followed by LTW-VLNT (n = 16) and SI-VLNT (n = 5). Lymph node harvest from the superficial inguinal region was associated with a significantly higher frequency of seroma development. Average percentage volume loss related in comparison to the preoperative volume of the affected limb was 9% after GE-VLNT, 10% after LTW-VLNT and 5% after SI-VLNT without a significant difference between the groups. PROMs revealed significant improvements for physical functioning, symptoms and psychological well-being, with no difference between VLNT techniques. CONCLUSIONS: VLNT leads to a significant improvement of quality of life and can effectively reduce limb volume, regardless of the selection of donor-site. GE-VLNT has become our flap of choice due to its low donor-site morbidity and its properties that allow a double transplantation while avoiding a second donor-site.

Primary Lymphovenous Anastomosis After Extended Soft Tissue Resection in the Medial Thigh for Reduction of Lymphocele and Lymphedema.

INTRODUCTION: Postoperative chronic lymphocele and lymphedema represent severe burdens for soft tissue sarcoma patients who are already physically handicapped after an extensive surgery and a long recovery time. Incidences are high in the upper medial thigh. We have shifted our focus to lymphedema and lymphocele risk reduction with immediate lymphovenous anastomosis (LVA) after sarcoma resection. METHODS: We performed immediate lymphatic reconstruction in 11 patients after soft tissue sarcoma resection in the upper medial thigh. The postoperative course was followed up closely, and postoperative occurrence of lymphocele and lymphedema was clinically assessed. A literature search outlining the latest clinical data, current treatment strategy landscape, and their application into clinical practice was added to the investigation. RESULTS: A total of 19 LVA and 2 lympho-lymphatic anastomoses were performed in 11 patients immediately after tumor resection in an end-to-end manner. We found a postoperative lymphedema rate of 36% and a postoperative lymphocele rate of 27%. Mean follow-up time was 17 months. Average tumor volume was 749 cc. Our literature search yielded 27 articles reporting on immediate LVA in cancer patients. Incidences of secondary lymphedema after LVA for lymphedema prevention vary between 0% and 31.1%. Lymphocele prevention with LVA is poorly studied in sarcoma patients. CONCLUSION: Immediate lymphatic reconstruction improved the overall postoperative course of our patients. The current literature does not serve with high-quality studies about primary LVA preventing lymphedema and lymphocele formation. We conclude that this technique should be seen as an additional concept to achieve overall better postoperative outcomes in these challenging surgical settings. We strongly recommend to either anastomose or ligate severed lymphatics under the microscope primarily after sarcoma resection in the upper medial thigh area.

100 anastomoses: a two-year single-center experience with robotic-assisted micro- and supermicrosurgery for lymphatic reconstruction.

Robotic-assisted microsurgery has gained significant attention in recent years following the introduction of two dedicated microsurgical robotic systems specifically designed for this purpose. These feature higher degrees of movement and motion scaling which are useful tools, especially when performing surgery in areas of the body which are difficult to access. Robotic-assisted microsurgery has been implemented in lymphatic surgery as well as soft tissue reconstructive surgery at our institution over the past 2.5 years. Our study gives an insight into the details and outcomes of the first 100 consecutive (super-) microsurgical anastomoses in peripheral and central lymphatic reconstruction performed with the Symani® Surgical System between 2021 and 2024. In total, 67 patients were treated, receiving robotic-assisted lymphatic reconstruction with lymphatic tissue transfer (LTT) and/or lymphovenous anastomoses (LVA)/lympholymphatic anastomoses (LLA). No anastomosis-associated complications were recorded postoperatively. The majority of patients reported a postoperative improvement of their lymphedema or central lymphatic disorder. In conclusion, we show the successful implementation of the Symani® Surgical System into our clinical practice of lymphatic reconstruction. Although the necessary intraoperative setup and the use of intrinsic motion scaling lead to a slight increase in operating time, the presented study demonstrates the advantages of robotic assistance which becomes particularly evident in lymphatic surgery due to the involved deep surgical sites and the need for supermicrosurgical techniques.

Arm lymphedema after vascularized lymph node harvest following Covid-19 vaccination.

There is evidence that COVID-19 vaccines may affect the lymphatic system. We report a case of a 40-year-old female who had undergone lymph node transfer for treating primary lymphedema of the legs. Six months later, the patient developed lymphedema of the right arm closely related to mRNA vaccination against COVID-19.

[Robotic-Assisted Lymphatic Surgery]. / Robotisch-assistierte Lymphchirurgie.

Surgical robotic systems specifically developed for microsurgery are increasingly being used in recent years, particularly in reconstructive lymphatic surgery. Currently, there are two robotic systems that are used in microsurgery. Both systems feature tremor reduction and motion scaling technologies, which are intended to optimise the surgeon's precision and dexterity. In the Department of Plastic Surgery and Hand Surgery at the University Hospital Zurich, the Symani Surgical System is used in many microsurgical and supermicrosurgical procedures. It is mainly used in reconstructive lymphatic surgery, especially for robotic-assisted lymphovenous anastomosis, microvascular anastomosis of lymph node flaps, and it is used in central lymphatic surgery. The robot enables smaller surgical approaches for deep anatomical structures with enhanced surgical precision. In combination with an exoscope, it can also improve the ergonomics of the microsurgeon.

CD112 Supports Lymphatic Migration of Human Dermal Dendritic Cells.

Dendritic cell (DC) migration from peripheral tissues via afferent lymphatic vessels to draining lymph nodes (dLNs) is important for the organism's immune regulation and immune protection. Several lymphatic endothelial cell (LEC)-expressed adhesion molecules have thus far been found to support transmigration and movement within the lymphatic vasculature. In this study, we investigated the contribution of CD112, an adhesion molecule that we recently found to be highly expressed in murine LECs, to this process. Performing in vitro assays in the murine system, we found that transmigration of bone marrow-derived dendritic cells (BM-DCs) across or adhesion to murine LEC monolayers was reduced when CD112 was absent on LECs, DCs, or both cell types, suggesting the involvement of homophilic CD112-CD112 interactions. While CD112 was highly expressed in murine dermal LECs, CD112 levels were low in endogenous murine dermal DCs and BM-DCs. This might explain why we observed no defect in the in vivo lymphatic migration of adoptively transferred BM-DCs or endogenous DCs from the skin to dLNs. Compared to murine DCs, human monocyte-derived DCs expressed higher CD112 levels, and their migration across human CD112-expressing LECs was significantly reduced upon CD112 blockade. CD112 expression was also readily detected in endogenous human dermal DCs and LECs by flow cytometry and immunofluorescence. Upon incubating human skin punch biopsies in the presence of CD112-blocking antibodies, DC emigration from the tissue into the culture medium was significantly reduced, indicating impaired lymphatic migration. Overall, our data reveal a contribution of CD112 to human DC migration.

A quadriphasic mechanical model of the human dermis.

The present study investigates the multiphasic nature of the mechanical behavior of human dermis. Motivated by experimental observations and by consideration of its composition, a quadriphasic model of the dermis is proposed, distinguishing solid matrix components, interstitial fluid and charged constituents moving within the fluid, i.e., anions and cations. Compression and tensile experiments with and without change of osmolarity of the bath are performed to characterize the chemo-mechanical coupling in the dermis. Model parameters are determined through inverse analysis. The computations predict a dominant role of the permeability in the determination of the temporal evolution of the mechanical response of the tissue. In line with the previous studies on other tissues, the analysis shows that an ideal model based on Donnan's equilibrium overestimates the osmotic pressure in skin for the case of very dilute solutions. The quadriphasic model is applied to predict changes in dermal cell environment and therefore alterations in what is called the "mechanome," associated with skin stretch. The simulations indicate that skin deformation causes a variation in several local variables, including in particular the electric field associated with a deformation-induced non-homogeneous distribution of fixed charges.

Lipidomic analysis of microfat and nanofat reveal different lipid mediator compositions.

BACKGROUND: Microfat and nanofat are two commonly used techniques in various surgical procedures from skin rejuvenation to scar correction that are known to contribute to tissue regeneration. While microfat mainly contains adipocytes and is well suited for tissue augmentation, nanofat is rich in lipids, adipose derived stem cells, microvascular fragments, and growth factors, making it attractive for esthetic use. We have previously demonstrated that the mechanical processing of microfat into nanofat significantly changes its proteomic profile. Considering that mechanical fractionation leads to adipocyte disruption and lipid release, we aimed to analyze the lipidomic profile for its regenerative properties. METHODS: Microfat and nanofat samples were isolated from fourteen healthy patients. Lipidomic profiling was performed by liquid chromatography tandem mass spectrometry. Resulting data was compared against the Human Metabolome and LIPID MAPS® Structure Database. Metaboanalyst was used to analyze metabolic pathways and lipids of interest. RESULTS: From 2,388 mass-to-charge ratio features, metabolic pathway enrichment analysis between microfat and nanofat samples revealed 109 pathways that were significantly enriched. While microfat samples revealed higher intensity levels of sphingosines, different eicosanoids and fat-soluble vitamins, increased levels of coumaric acids and prostacyclin were found in nanofat. CONCLUSIONS: This is the first study that has analyzed the lipidomic profile of micro- and nanofat, providing evidence that mechanical emulsification of microfat into nanofat leads to changes in their lipid profile. From 109 biological pathways, anti-inflammatory, anti-fibrotic and anti-melanogenic lipid mediators were particularly enriched in nanofat samples when compared to microfat. Although further studies are necessary to have a deeper understanding on the composition of these specific lipid mediators in nanofat samples, we propose that they might contribute to its regenerative effects on tissue.

Thromboembolic events in burn patients: An analysis of risk factors and different anticoagulants.

BACKGROUND: Burn patients are in a state of activated coagulation, putting them at risk for thromboembolic events. Additionally, certain patient-related factors are associated with an increased risk of thrombus formation. This study aimed to evaluate the incidence of thromboembolic events and identify potential risk factors, including patient characteristics, surgical treatment, anticoagulation strategies, and laboratory parameters. METHODS: A single-centre retrospective cohort study was conducted on all patients with burns treated between 2002 and 2020. Medical reports of patients with and without thromboembolic events were descriptively analysed. The association of time to thromboembolic events with total body surface area (TBSA) was assessed by cause-specific Cox models adjusted for different covariates. The association of time to thromboembolic events with type and dosage of anticoagulants was assessed using a cause-specific Cox proportional hazards model with time-dependent covariates, applied to a matched subset of patients. RESULTS: The incidence of thromboembolic events was 8.1% in a cohort of 642 patients. We found a statistically significant increase in the hazard for thromboembolic events by a factor of 1.02 (95% CI 1.00 to 1.03; P ≤ 0.05) per percent increase in TBSA. We identified former alcohol abuse (HR=2.54, CI 1.33 to 4.84, P = 0.005) and higher body mass index (HR=1.06, 95% CI 1.00 to 1.12, P = 0.046) as potential risk factors for the development of thromboembolic events. We further noted inadequate median anti-Factor-X activity levels and elevated C-reactive protein and procalcitonin levels at the time of the event. CONCLUSION: Our results showed a moderate risk of thromboembolic events among burn patients, underlining the importance of close monitoring with regard to thrombus formation. In particular, patients with higher TBSA, alcohol abuse and BMI may be evaluated more regularly for thromboembolic events. Anti-Factor-X activity levels should be determined regularly and therapy should be adjusted if necessary.

Prevalence and Prognostic Role of Lymphedema in Patients with Deep Venous Thrombosis and Thrombophlebitis.

Background: Deep venous thrombosis (DVT) poses a substantial disease burden. Lymphedema may present with similar symptoms making the diagnosis process more difficult. Data on the epidemiology of lymphedema are lacking. Methods: The German nationwide inpatient sample served to analyze all patients hospitalized owing to DVT and/or thrombophlebitis (referred to as DVT) of the legs in Germany between 2005 and 2020. We stratified these patients for additional lymphedema and analyzed the impact of lymphedema on adverse in-hospital events. Results: Overall, 1,136,574 hospitalizations related to DVT were recorded in Germany during 2005-2020 (53.3% women; 51.3% aged ≥70 years). Lymphedema was coded in 9974 (0.9%) patient-cases (82.0% not elsewhere classified, 17.7% secondary lymphedema). Annual numbers of hospitalizations with lymphedema among DVT patients increased from 450 (2005) to 613 (2016) (ß 0.57; 95% confidence interval [CI]: 0.48-0.66], p < 0.001) and decreased thereafter. Despite similar age, DVT patients with lymphedema had higher prevalence of cardiovascular diseases, chronic organ failure, and all types of investigated cancer. Prevalence of pulmonary embolism (PE) with shock/CPR (4.1% vs. 1.5%), acute renal failure (6.7% vs. 2.5%), and stroke (5.2% vs. 4.2%) was higher in DVT patients with lymphedema than without. Lymphedema was independently associated with PE with shock/CPR (OR: 2.1; 95% CI: 1.9-2.3) as well as death (OR: 1.3; 95% CI: 1.2-1.4). Conclusions: Comorbidity conditions like cancer, obesity, and cardiovascular risk factors, and also infectious complications, were more prevalent in DVT patients with lymphedema than in those without. Lymphedema was independently associated with severe in-hospital complications, particularly when its genesis was related to severe comorbidities.

Robotic Microsurgery in Extremity Reconstruction - Experience With a Novel Robotic System.

Background: Robotic systems have successfully been introduced into other surgical fields in the past. First attempts with different setups are made in the field of microsurgery. The Symani® Surgical System, a flexible platform consisting of two robotic arms, features motion scaling with tremor filtration to address the demands and complexity of microsurgery. Symani's NanoWrist Instruments are the world's smallest, wristed surgical instruments, intended to improve a surgeon's range of motion beyond the capability of the human hand. This combination allows surgeons to scale their hand movements while seamlessly articulating the robotic micro instruments. Purpose: We report on our experience in extremity reconstruction with this novel system.Research Design: The Symani Surgical System® was used for 6 cases of extremity reconstruction. The surgeon controlled the manipulators along with the footswitch while either sitting away from the operating table relying on 3D visualization with an exoscope or sitting at the operating table using a standard microscope.Data Collection: Microsurgical anastomoses were performed in 4 patients (3 end-to-end arterial anastomoses and one end-to-side arterial anastomosis) and nerve grafting was performed in 2 patients.Results: Microvascular anastomoses were slower vs conventional microsurgery, but all anastomoses were patent. Epineural coaptation showed proper fascicle alignment and tissue manipulation could be kept to a minimum. The platform's motion scaling allows the surgeon to perform precise micro-movements with only minimal tissue manipulation and hard-to-reach anatomy becomes accessible more easily.Conclusions: Robotic microsurgery might gain importance in the nearer future but more data will need to be collected.

Impact of a High-Fat Diet at a Young Age on Wound Healing in Mice.

As the prevalence of juvenile-onset obesity rises globally, the multitude of related health consequences gain significant importance. In this context, obesity is associated with impaired cutaneous wound healing. In experimental settings, mice are the most frequently used model for investigating the effect of high-fat diet (HFD) chow on wound healing in wild-type or genetically manipulated animals, e.g., diabetic ob/ob and db/db mice. However, these studies have mainly been performed on adult animals. Thus, in the present study, we introduced a mouse model for a juvenile onset of obesity. We exposed 4-week-old mice to an investigational feeding period of 9 weeks with an HFD compared to a regular diet (RD). At a mouse age of 13 weeks, we performed excisional and incisional wounding and measured the healing rate. Wound healing was examined by serial photographs with daily wound size measurements of the excisional wounds. Histology from incisional wounds was performed to quantify granulation tissue (thickness, quality) and angiogenesis (number of blood vessels per mm2). The expression of extracellular matrix proteins (collagen types I/III/IV, fibronectin 1, elastin), inflammatory cytokines (MIF, MIF-2, IL-6, TNF-α), myofibroblast differentiation (α-SMA) and macrophage polarization (CD11c, CD301b) in the incisional wounds were evaluated by RT-qPCR and by immunohistochemistry. There was a marked delay of wound closure in the HFD group with a decrease in granulation tissue quality and thickness. Additionally, inflammatory cytokines (MIF, IL-6, TNF-α) were significantly up-regulated in HFD- when compared to RD-fed mice measured at day 3. By contrast, MIF-2 and blood vessel expression were significantly reduced in the HFD animals, starting at day 1. No significant changes were observed in macrophage polarization, collagen expression, and levels of TGF-ß1 and PDGF-A. Our findings support that an early exposition to HFD resulted in juvenile obesity in mice with impaired wound repair mechanisms, which may be used as a murine model for obesity-related studies in the future.

First-in-human Use of a Microsurgical Robotic System for Central Lymphatic Reconstruction.

Advances in the development of robotic systems have recently enabled the use of robotic technology in reconstructive lymphatic surgery. Although the advantages of microsurgical robots must be weighed carefully against the costs, their use may allow for smaller surgical approaches and easier access to anatomically deeper structures or even smaller vessels. We report on a case of a patient with central lymphatic dilation causing abdominal pain and severely reduced physical capacity. Sonography-assisted intranodal injection of indocyanine green allowed for localization of the lymphatic cyst and anastomosis with the left ovarian vein, applying robotic-assisted microsurgery for the first time on the central lymphatic system. Following the successful reconstruction of lymphatic drainage and decompression of the cyst, the patient reported a complete regression of her preoperative symptoms. From a surgical point of view, the Symani Surgical System improved precision and allowed significantly smaller surgical access. Considering the high morbidity and rarity of pathologies of the central lymphatic system, central lymphatic surgery is to date rarely performed. With improved precision and significantly smaller surgical access, robotic-assisted microsurgery has great potential to expand the treatment options for central lymphatic lesions.

Involvement of the Macrophage Migration Inhibitory Factor (MIF) in Lipedema.

Lipedema is a chronic disorder that mainly affects women. It is often misdiagnosed, and its etiology remains unknown. Recent research indicates an accumulation of macrophages and a shift in macrophage polarization in lipedema. One known protein superfamily that contributes to macrophage accumulation and polarization is the macrophage migration inhibitory factor (MIF) family. MIF-1 and MIF-2 are ubiquitously expressed and also regulate inflammatory processes in adipose tissue. In this study, the expression of MIF-1, MIF-2 and CD74-a common receptor for both cytokines-was analyzed in tissue samples of 11 lipedema and 11 BMI-matched, age-matched and anatomically matched control patients using qPCR and immunohistochemistry (IHC). The mRNA expression of MIF-1 (mean 1.256; SD 0.303; p = 0.0485) and CD74 (mean 1.514; SD 0.397; p = 0.0097) were significantly elevated in lipedema patients, while MIF-2 expression was unaffected (mean 1.004; SD 0.358; p = 0.9718). The IHC analysis corroborated the results for CD74 expression on a cellular level. In conclusion, our results provide first evidence for a potential involvement of the MIF family, presumably via the MIF-1-CD74 axis, in lipedema.

Basic Principles in the Management of Acute Burn Injuries in Adults.

INTRODUCTION: This review outlines an overview of up-to-date, stage-appropriate treatment methods for burn injuries as practiced at the National Burn Center of the University Hospital Zurich. It intends to provide practitioners with recommendations for the management of acute minor to severe burn injuries based on scientific evidence as well as the long-term experience of the Burn Center. The focus is on a practical guideline and various options including novel, innovative conceptual approaches.

Human amniotic membranes as an allogenic biological dressing for the treatment of burn wounds: Protocol for a randomized-controlled study.

Background: Burn wounds pose significant challenges in medical treatment due to their devastating nature and resource-intensive requirements. Temporary coverage of burn wounds using synthetic or biological dressings allows for reepithelization before definitive skin grafting. Allogenic skin grafts have been widely used but come with drawbacks such as rejection and disease transmission. The use of amniotic membranes (AMs) offers a promising alternative for temporary coverage, as they possess biological properties that promote faster healing and improved scar quality. The various components of the amniotic membrane, including pluripotent stem cells, extracellular matrix proteins, and regenerative factors, contribute to cell growth, migration, and differentiation, as well as preservation of the original epithelial phenotype. Objective: Reliable information on the treatment of burn wounds with AM is needed. The knowledge gained in this project may help to include this advantageous modern concept of biological dressings in clinical practice. The purpose of this study is to use human amniotic membranes from our in hospital laboratory, as an allogenic biological dressing after enzymatic debridement in superficial partial thickness, deep partial thickness or full thickness burn wounds. Methods: We will include 30 patients in a randomized-controlled trial with each patient receiving the study intervention and the control intervention. Two 7 × 7 cm burn wound areas will be compared regarding percentage of skin graft take, healing time, healing percentage value and total healing time. Human amniotic membranes will be compared to allogenic skin grafts.

Benefits of robotic-assisted lymphatic microsurgery in deep anatomical planes.

Micro- and supermicrosurgeries have become standard techniques for lymphatic reconstruction. As increasingly smaller vessels are being targeted, robotic-assisted surgery has emerged as a new approach to push reconstructive limits owing to its ability of motion scaling and providing better accessibility of deep anatomical regions. The precision of the robot is achieved at the expense of operating speed among other variables; therefore, the surgeon must weigh the enhanced dexterity against the additional operating time and cost required for the robotic surgical system itself to ensure optimal resource utilization. Here we present a case series of 8 patients who underwent robot-assisted lymphatic microsurgery for omental flap transfer to the axilla and lympho-venous anastomosis. The Symani® Surgical System was used with a conventional microscope or 3D exoscope. The use of 3D exoscope provided clear benefits in terms of surgeon positioning. Moreover, access to the recipient vessels near the thoracic wall was significantly improved with the robotic setup. In addition, suture precision was excellent, resulting in patent anastomoses. Operating time for anastomosis was comparable to that for manual anastomosis and demonstrated a steep learning curve. The benefits of robotic systems in operating fields with good exposure require further evaluation. However, owing to longer instruments, additional stability, dexterity, and motion precision, robotic systems offer a marked advantage for operating in deep anatomical planes and on small structures. A potentially new field for the implementation of robotic surgery is central lymphatic reconstruction. Progress in terms of operating time and cost is crucial, and future research should validate the effectiveness of robotic-assisted surgery in larger clinical studies.

Multiscale mechanical analysis of the elastic modulus of skin.

The mechanical properties of the skin determine tissue function and regulate dermal cell behavior. Yet measuring these properties remains challenging, as evidenced by the large range of elastic moduli reported in the literature-from below one kPa to hundreds of MPa. Here, we reconcile these disparate results by dedicated experiments at both tissue and cellular length scales and by computational models considering the multiscale and multiphasic tissue structure. At the macroscopic tissue length scale, the collective behavior of the collagen fiber network under tension provides functional tissue stiffness, and its properties determine the corresponding elastic modulus (100-200 kPa). The compliant microscale environment (0.1-10 kPa), probed by atomic force microscopy, arises from the ground matrix without engaging the collagen fiber network. Our analysis indicates that indentation-based elasticity measurements, although probing tissue properties at the cell-relevant length scale, do not assess the deformation mechanisms activated by dermal cells when exerting traction forces on the extracellular matrix. Using dermal-equivalent collagen hydrogels, we demonstrate that indentation measurements of tissue stiffness do not correlate with the behavior of embedded dermal fibroblasts. These results provide a deeper understanding of tissue mechanics across length scales with important implications for skin mechanobiology and tissue engineering. STATEMENT OF SIGNIFICANCE: Measuring the mechanical properties of the skin is essential for understanding dermal cell mechanobiology and designing tissue-engineered skin substitutes. However, previous results reported for the elastic modulus of skin vary by six orders of magnitude. We show that two distinct deformation mechanisms, related to the tension-compression nonlinearity of the collagen fiber network, can explain the large variations in elastic moduli. Furthermore, we show that microscale indentation, which is frequently used to assess the stiffness perceived by cells, fails to engage the fiber network, and therefore cannot predict the behavior of dermal fibroblasts in stiffness-tunable fibrous hydrogels. This has important implications for how to measure and interpret the mechanical properties of soft tissues across length scales.