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 of all patients undergoing 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 (gastroepiploic [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. There were 49 patients who underwent GE-VLNT, followed by LTW-VLNT (n = 16) and SI-VLNT (n = 5). Lymph node harvest from the SI was associated with a significantly higher frequency of seroma development. The 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 differences between the VLNT techniques. CONCLUSIONS: VLNT leads to a significant improvement of quality of life and can decrease limb volume effectively, regardless of the selection of donor site. GE-VLNT has become our flap of choice owing to its low donor site morbidity and its properties that allow a double transplantation while avoiding a second donor site.

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 .

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.

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.

[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.

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.

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.

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.

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.

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.

PROMs after Lymphatic Reconstructive Surgery: Is There a Correlation between Volume Reduction and Quality of Life?

Patients with upper limb lymphedema and lower limb lymphedema experience a wide range of physical and psychological symptoms that affect quality of life. The benefits of lymphatic reconstructive surgery for patients with lymphedema are undisputed. However, recording volume reduction alone may be insufficient with regard to postoperative outcome because measurements are often inadequate, depend on many factors, and do not reflect improvement in quality of life. Methods: We conducted a prospective single center study patients receiving lymphatic reconstructive surgery. Patients received volume measurements preoperatively and at standardized postoperative intervals. To evaluate patient-reported outcomes, patients completed the following questionnaires: LYMPH-Q Upper Extremity Module, quickDASH, SF 36, Lymphoedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphoedema, and Lower Extremity Functional Scale at the aforementioned intervals. Results: We included 55 patients with upper limb lymphedema (24%) and lower limb lymphedema (73%) of lymphedema grades I-III. Patients received lymphovenous anastomosis only (23%), free vascularized lymph node transfer (35%) or a combination of both (42%). Analysis of patient-reported outcome measurements revealed improvements with respect to a broad range of complaints, particularly physical function, symptoms, and psychological well-being. There was no correlation between the extent of volume reduction and improvement in quality of life (Pearson correlation coefficient below ±0.7; P > 0.05). Conclusions: Based on a broad range of outcome measurements, we observed an improved quality of life in almost all patients, even in those without measurable volume loss of the extremity operated on, which emphasizes the need for a standardized use of patient-reported outcome measures to evaluate the benefits of lymphatic reconstructive surgery.

A Comparative Analysis to Dissect the Histological and Molecular Differences among Lipedema, Lipohypertrophy and Secondary Lymphedema.

Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses.

[Robotics in plastic surgery]. / Robotik in der plastischen Chirurgie.

In recent years surgical robotic systems which were specifically developed for microsurgery have expanded the application of robotic-assisted surgery to plastic reconstructive surgery. Currently, there are two microsurgical robotic systems available for reconstructive plastic surgery. Both systems feature tremor reduction and motion scaling technologies, which are intended to optimize the surgeon's precision and dexterity. In the Department of Plastic Surgery and Hand Surgery at the University Hospital Zurich, the Symani Surgical System® has already been used for many microsurgical and supermicrosurgical operations, including autologous breast reconstruction, nerve transfer and, in particular, reconstructive lymphatic surgery. Despite special technical challenges, such as a lack of haptic feedback, the advantages outweigh the disadvantages for an appropriately trained and skilled microsurgeon, including smaller surgical access incisions for anatomically deep structures and an improvement in surgical precision.

Enzymatic debridement for circumferential deep burns: the role of surgical escharotomy.

INTRODUCTION: Circumferential deep burns carry a high risk for a burn induced compartment syndrome. It was recently shown that an enzymatic bromelain-based debridement with Nexobrid® is a safe and efficient procedure to release pressure in deep circumferential extremity burns reducing the need for surgical escharotomy. We therefore herein aimed to analyze the conceptual relation between Nexobrid® and surgical escharotomy. PATIENTS AND METHODS: We conducted a retrospective study on all patients with circumferential deep partial-thickness or full-thickness burns requiring immediate escharotomy that was either performed by surgical incision or Nexobrid®. Medical records of 792 patients that were treated at the burn center of the University Hospital Zurich between 2016 and 2021 were analyzed. RESULTS: Overall, 62 patients with circumferential deep partial-thickness or full-thickness burns who received preventive decompression either by Nexobrid® (N = 29) or surgical escharotomy (N = 33), were included. Whilst distribution of age, sex, BMI and type of injury showed no difference between the groups, the ABSI score, TBSA, percentage of third degree burns and mortality were significantly higher in patients who received a surgical escharotomy. CONCLUSION: While the use of Nexobrid® to prevent burn induced compartment syndrome has steadily increased, surgical escharotomies were predominantly performed in severely burned patients with a high degree of full-thickness burns. Thus, higher mortality in this patient group needs to be considered with caution and is mainly attributed to the higher TBSA. Although evidence is lacking for the use of Nexobrid® for larger body areas exceeding 15%, escharotomy is also the more reliable and faster approach in such critically burned patients.

Scar versus shape: patient-reported outcome after different surgical approaches to gynecomastia measured by modified BREAST Q®.

OBJECTIVES: The challenge in the operative therapy for enlargement of the male breast is to deal with the skin excess. Shape and scars are the major parameters after which patients assess their operative result. Therefore, we assessed the satisfaction rate among patients undergoing subcutaneous mastectomy at our institution with special regard to scar tissue formation and the postoperative appearance of the chest wall in dependence of the surgical approach (periarolar versus inframammary fold). METHODS: The study includes n = 36 male patients who underwent subcutaneous mastectomy at AGAPLESION Markus Hospital Frankfurt/Main. Patient's satisfaction dependent with the appearance of the chest wall and scar formation was evaluated by a modified BREAST Q® questionnaire plus two male-based additional questions. RESULTS: There is no statistically significant difference in satisfaction with the operative result depending on the pattern of incision (periareolar versus submammary periareolar; 81.9% versus 75.5%) with the operative result. Evaluation of additional questions of the modified BREAST Q® questionnaire showed that 86% of the patients (n = 31) would rather have more scars and a flatter chest wall. A BMI >25 kg/m2 is accompanied by a higher risk for complications (p = 0.04). CONCLUSIONS: Periareolar incision is still the method of choice, if promising an aesthetic appealing result. When reaching its limits though, we showed that a flat and male-shaped appearance of the chest wall is priority for the patients and should therefore be for the surgeon as well.

Botulinum toxin to improve facial expression in a patient with Urofacial (Ochoa) Syndrome.

The Urofacial or Ochoa Syndrome is a very rare congenital disorder that includes vesical bladder dysfunction and a peculiar inverse facial expression, which brings patients to express a sad-crying face while they intend to laugh. Up-to-date treatments have addressed only the urological side of this disease. However, also the impaired facial mimicry has a strong impact on patients' quality of life. We treated a young patient with Botulinum toxin to address this impairment and obtained pleasing results, including a harmonic smile and a very satisfied patient. To the best of our knowledge, this is the first time that the use of Botulinum toxin is reported in literature to address the facial expression component of this disease.

Is Lymphedema a Systemic Disease? A Paired Molecular and Histological Analysis of the Affected and Unaffected Tissue in Lymphedema Patients.

Secondary lymphedema is a chronic, debilitating disease and one of the most common side effects of oncologic surgery, substantially decreasing quality of life. Despite the progress conducted in lymphedema research, the underlying pathomechanisms remain elusive. Lymphedema is considered to be a disease affecting an isolated extremity, yet imaging studies suggest systemic changes of the lymphatic system in the affected patients. To evaluate potential systemic manifestations in lymphedema, we collected matched fat and skin tissue from the edematous and non-edematous side of the same 10 lymphedema patients as well as anatomically matched probes from control patients to evaluate whether known lymphedema manifestations are present systemically and in comparison to health controls. The lymphedematous tissue displayed various known hallmarks of lymphedema compared to the healthy controls, such as increased epidermis thickness, collagen deposition in the periadipocyte space and the distinct infiltration of CD4+ cells. Furthermore, morphological changes in the lymphatic vasculature between the affected and unaffected limb in the same lymphedema patient were visible. Surprisingly, an increased collagen deposition as well as CD4 expression were also detectable in the non-lymphedematous tissue of lymphedema patients, suggesting that lymphedema may trigger systemic changes beyond the affected extremity.

Exploring the learning curve of a new robotic microsurgical system for microsurgery.

Robotic systems have recently been introduced into micro- and supermicrosurgery showing potential benefits for reconstructive surgery. After showing the feasibility and safety of using the Symani Surgical System® for lymphatic microsurgical procedures in humans, we present the results of the first twenty-two patients operated with the robot. The main goal of the study was to determine the learning curve using the Symani Surgical System® . In addition, we aimed at exploring the potential of robot-assisted anastomosis for lymphatic, free flap, and nerve reconstruction and defining the advantages and drawbacks of implementing the system into our daily routine. The operating times were compared between robotic-assisted and hand-sewn anastomoses. Moreover, outcomes and complications were recorded. In this first patient series, anastomotic times were significantly faster with the hand-sewn technique (14.1±4.3 min) when compared with the robot-assisted technique (25.3±12.3 min; p<0.01). However, the learning curve was very steep, and the time needed to perform the anastomosis has been consistently decreasing over time to the point where in the last operations, the times to perform particularly lympho-venous anastomoses were comparable between the two groups. Based on our experience up to date, robot-assisted surgery shows a promising potential in opening up new frontiers in reconstructive microsurgery, e.g., the reliable performance of anastomoses on even smaller blood and lymphatic vessels or on structures deeper within the body cavities, e.g., the thoracic duct.

Protein Profiling of Mechanically Processed Lipoaspirates: Discovering Wound Healing and Antifibrotic Biomarkers in Nanofat.

BACKGROUND: Nanofat is an injectable oily emulsion, rich in adipose-derived stem cells and growth factors. It is prepared from lipoaspirates through mechanical emulsification and filtration. Despite being successfully used in several procedures in regenerative medicine such as scar attenuation, skin rejuvenation, and treatment of chronic wounds, little is known about exactly how nanofat induces regeneration in treated skin at the molecular level. METHODS: Microfat and nanofat samples were isolated from 18 healthy patients. Proteomic profiling was performed through untargeted mass spectrometry proteomics and multiplex antibody arrays. Pathway enrichment analysis of differentially expressed proteins between microfat and nanofat was performed using Gene Ontology, Reactome, and Kyoto Encyclopaedia of Genes and Genomes as reference databases. RESULTS: Untargeted proteomics showed that up-regulated genes in nanofat are involved in innate immunity responses, coagulation, and wound healing, whereas down-regulated genes were linked to cellular migration and extracellular matrix production. Secretome array screening of microfat and nanofat samples showed no significantly different expression, which strongly suggests that the mechanical emulsification step does not affect the concentration of tissue regeneration biomarkers. The identified proteins are involved in wound healing, cellular migration, extracellular matrix remodeling, angiogenesis, stress response, and immune response. CONCLUSIONS: Mechanical processing of lipoaspirates into nanofat significantly influences the proteome profile by enhancing inflammation, antimicrobial, and wound healing pathways. Nanofat is extremely rich in tissue repair and tissue remodeling factors. This study shows that the effects of microfat and nanofat treatment are based on up-regulated inflammation, antimicrobial, and wound healing pathways. Mechanical emulsification does not alter the concentration of tissue regeneration biomarkers. CLINICAL RELEVANCE STATEMENT: In addition to adipose-derived stems cells, nanofat contains distinct tissue repair and remodelling factors, which explains its beneficial effects on tissue regeneration.