Does Lymphovenous Anastomosis Effect Mammalian Target of Rapamycin Inhibitor-associated Lymphedema Patients?

The mammalian target of rapamycin (mTOR) inhibitors are used to prevent organ transplant rejection and are preferred over other immunosuppressants due to its low nephrotoxicity. However, mTOR inhibitors have been associated with various adverse effects including lymphedema. Although rare in incidence, previously known treatments for mTOR inhibitor-induced lymphedema were limited to discontinuation of related drugs and complex disruptive therapy with variable results. In this article, three patients who developed lymphedema in their lower limbs after using mTOR inhibitors, including two bilateral and one unilateral case, were treated with physiologic surgery methods such as lymphovenous anastomosis (LVA) and lymph node transfer. The efficacy of the treatment was evaluated. In the three cases described, cessation of the drug did not lead to any reduction in edema. The use of LVA and lymph node transfer resulted in early reductions in volume but failed to sustain over time. All patients underwent secondary nonphysiologic surgery such as liposuction resulting in sustained improvement. This series presents the first physiologic approach to mTOR inhibitor-induced lymphedema. Although further study is warranted, the physiologic surgical options may have limited success and nonphysiologic options may offer better sustainable results.

Lipedema associated with Skin Hypoperfusion and Ulceration: Soft Tissue Debulking Improving Skin Perfusion.

Lipedema is a progressive connective tissue disease with enlargement of adipose tissue, fibrosis, fluid collection, and dermal thickening. Herein, we present a case of lipedema associated with skin hypoperfusion and ulceration in which soft tissue debulking with liposuction improved patients' symptoms. A 39-year-old female presented with asymmetric progressive initially unilateral lower limb swelling with severe pain with subsequent skin ulceration. Conservative management failed to improve her condition. After excluding other causes and detailed radiologic investigation, lipedema was diagnosed with an associated impaired skin perfusion. Trial of local wound care and compression therapy failed to improve the condition. Subsequent soft tissue debulking with circumferential liposuction and ulcer debridement and immediate compression showed dramatic improvement of the symptoms and skin perfusion. The unique nature of this case sheds light on lipedema as a loose connective tissue disease. Inflammation and microangiopathies explain the associated pain with hypoperfusion and ulceration being quite atypical and in part might be related to the large buildups of matrix proteins and sodium contents leading to fragility in microvessels with frequent petechiae and hematoma and subsequent tissue ischemia. Conservative measures like compression therapy plays a significant role in disease course. Surgical debulking with liposuction was shown to be efficacious in reducing the soft tissue load with improvement in limb pain, edema, circumference, and skin perfusion that was seen in our patient. Lipedema is a frequently misdiagnosed condition with disabling features. Skin involvement in lipedema with potential hypoperfusion was shown and it requires further investigation.

[Free thin anterolateral thigh flap in head and neck surgery]. / Vékonyított perforátor comblebeny alkalmazása szabad szövetpótlásra a fej-nyaksebészetben.

Elorehaladott szájüregi daganatok eltávolítása után kialakult kiterjedt szövethiányok helyreállítására funkciómegtartó céllal a leggyakrabban alkalmazott eljárás a mikrovaszkuláris technikával végzett szabad szövetátültetés. Hazánkban a felületes szájüregi hiányok helyreállítására a leggyakrabban választott szabadlebeny a radiális alkarlebeny. Elsosorban vastagabb vagy nagyobb kiterjedésu hiányokra alkalmazzuk az anterolateralis comblebenyt. Az alkarlebeny esetén azonban a donorterületi szövodményráta jóval magasabb. Vékonyított anterolateralis comblebeny a hátrányokat kiiktatva alkalmas lehet az alkarlebeny intraoralis alkalmazása helyett.A korábban nyelvtumor miatt operált, alkarlebennyel rekonstruált és besugarazott 69 éves nobetegnél a korábbi mutéti terület szélén a követéses kontrollvizsgálat során recidív tumort verifikáltunk. Az Onkoterápiás Bizottság döntését követoen a recidíva eltávolítását, tangencionális mandibula reszekciót és szabad lebenyes helyreállítást terveztünk tracheotomiás védelemben. Elozetes kézi dopplerrel és duplex ultrahanggal történo perforátor meghatározás után, a jobb combon a perforátorra centrálva 6 × 8 cm-es superficialis fascia rétegében vékonyított anterolateralis comblebenyt preparáltunk. A lebeny vastagsága 6-8 mm, az érnyél hossza 12 cm volt, mely az intraoralis hiányra ideális volt. A nyakon elkészített mikrosebészeti anasztomózis után a donorterületet primeren zártuk.A lebeny keringése mindvégig kielégíto volt. A tracheotomiát a posztoperatív 11. napon megszüntettük, perorális táplálkozása a posztoperatív 14. napon helyreállt.Az anterolateralis comblebeny sokrétusége az anatómiájában rejlik. A korábban csak nagyobb és vastagabb hiányokra használt anterolateralis comblebeny jó adaptálhatósága és megfelelo mérete miatt felületesebb hiányokra is alkalmas. A korábban alkarlebennyel helyreállított hiányok pótlására a hasonló tulajdonságokkal rendelkezo vékonyított anterolateralis comblebeny is alkalmazható azzal a jelentos elonyével együtt, hogy a donorhely morbiditása minimális az alkarlebennyel szemben.

How to Start and Build Microsurgery Practice-Topics on Success and Sustainability: Global/International.

Many young microsurgeons begin their careers at established hospitals where microsurgery resources are limited. This article shares the authors' experiences in overcoming challenges and establishing a microsurgery practice in a new hospital. Due to the lack of equipment, limited support from colleagues, absence of discussion partners, fear of failure, and unpredictable situations, many aspiring microsurgeons lose their motivation. The purpose of this article is to guide future microsurgeons by describing the author's actions and suggesting improvements for their first free flap case. Key factors for building a successful, sustainable, and enjoyable microsurgery practice include remembering your training and mentors, acquiring fundamental knowledge of microsurgery, creating a supportive ecosystem, and having fun.

Identifying Functional Lymph Nodes in Lower Extremity Lymphedema Patients: The Role of High-frequency Ultrasound.

BACKGROUND: Lymph nodes may play a potential role in lymphedema surgery. Radiologic evaluation of nodes may reveal the status of pathologic conditions but with limited accuracy. This study is the first to evaluate the efficacy of ultrasound in detecting functioning nodes in lymphedema patients and presents a criterion for determining the functionality of the lymph nodes. METHODS: This retrospective study reviews 30 lower extremity lymphedema cases which were candidates for lymph node to vein anastomosis. Lymphoscintigraphy and magnetic resonant lymphangiography (MRL) imaging were compared with ultrasound features which were correlated to intraoperative indocyanine green (ICG) nodal uptake as an indication of functionality. RESULTS: Majority were International Society of Lymphology stage 2 late (50.0%) and stage 3 (26.7%). ICG positive uptake (functioning nodes) was noted in 22 (73.3%), while 8 patients (26.6%) had negative uptake (nonfunctioning). Ultrasound had significantly the highest specificity (100%) for identifying functional nodes followed by lymphoscintigraphy (55%) and MRL (36%; p = 0.002, p < 0.001, respectively). This was associated with 100% positive predictive value compared against lymphoscintigraphy (44%) and MRL (36%; p < 0.001 for both). The identified ultrasound imaging criteria for functioning lymph node were oval lymph node shape (Solbiati Index), morphology, vascularity pattern, and vascularity quantification. CONCLUSION: The use of ultrasound in nodal evaluation was proven effective in different pathologic conditions and demonstrated the best prediction for functionality of the lymph node based on the new evaluation criteria.

Effects of an Ultra-Polished Scalpel on Incisional Wounds in a Diabetic Model.

Inflammation after surgical incisions is related to the degree of tissue damage. Healing with low inflammation is desirable, especially in patients with compromised healing potential. This experimental study was conducted to assess the degree of inflammatory reaction and scar formation from incisions made by an ultra-polished scalpel (UPS). Two paravertebral incisions were made with a conventional scalpel (CS) and a UPS in 18 individual rats with diabetes. The fibrotic tissue (scar) area and expression levels of collagen, transforming growth factor, and matrix metalloproteinases were quantified on postoperative days 3, 7, and 30. The scar widths and areas were significantly lower in the UPS group than in the CS group. The scar widths were 64.3 ± 14.7 µm and 86.8 ± 12.1 µm in the UPS and CS groups, respectively (P = 0.03). The scar areas were 11,398 ± 1595 µm2 in the UPS group and 17,433 ± 3487 µm2 in the CS group (P = 0.014). The UPS group had less inflammation on day 3, less transforming growth factor synthesis on days 3 and 7, lower levels of matrix metalloproteinases, and less collagen synthesis on day 7 than did the CS group. The UPS achieved less local inflammation by reducing the local tissue damage in diabetic rat models, enabling better healing, and resulting in less scar formation. The UPS warrants further clinical study as it may bring beneficial outcomes for patients with impaired healing capability and patients who seek to reduce scarring.

Application of a Microsuction Background Device for Microanastomosis in a Rat Femoral Vessel Model.

SUMMARY: Microvascular anastomoses can be challenging to perform when edematous fluids and blood continuously flood and compromise the field of view. Intermittent irrigation and suctioning disturb workflow, require an assistant, and can increase risk of arterial thrombosis from vessels being drawn into suction drains. The authors developed and patented a novel three-dimensionally printed background device with microfluidic capabilities to provide autonomous, continuous irrigation and suction to optimize operator autonomy and efficiency. The authors tested this in a rat femoral vessel model. Twelve end-to-end anastomoses were performed by two senior microsurgeons [six conventional, six suction-assisted background (SAB)] in a rat femoral artery model. The primary outcome was time taken to complete the anastomosis. Secondary outcomes included the validated Structured Assessment of Microsurgery Skills (SAMS) score and the total number of "wiping" events to obtain field clarity. Each procedure was recorded, and videos were independently rated by two blinded experts using the SAMS score. Time taken to complete the anastomosis was greater in the conventional group compared with the SAB group (741.7 ± 203.1 seconds versus 584 ± 155.9 seconds; P = 0.007). The median SAMS score was lower in the conventional group compared with the SAB group (32.3 ± 1.4 versus 38.3 ± 1.5; P = 0.001). The median number of wiping events was significantly greater in the conventional group compared with the SAB group (13 ± 2.2 versus 1.7 ± 1.2; P < 0.001). The authors show that a novel microfluidic background device allows continuous irrigation and suctioning without the need for an assistant, optimizing the efficiency of the microvascular anastomosis. CLINICAL RELEVANCE STATEMENT: The authors have designed a novel, patented, three-dimensionally printed microsurgical background device that provides continuous irrigation and suction, reduces operative time, and provides better vessel clarity during a microsurgical anastomosis compared to standard background.

Soft Tissue Reconstruction After Revascularization.

Diabetic foot ulcer represents the primary cause of hospital admissions, amputations, and mortality in diabetic patients. The development of diabetic foot ulcers is influenced by peripheral neuropathy, infection, and ischemia, with diabetes contributing to peripheral artery disease. Free tissue transfer combined with revascularisation of the lower extremity provides the potential opportunity for limb salvage in individuals with lower extremity defects due to critical limb ischemia and diabetic foot.

Effect of a portable light emitting diode device on wound healing in a rat model.

Light-emitting diode (LED) lights produce a variety of wavelengths that have demonstrable efficacy in therapeutic and aesthetic fields. However, a repetitive treatment regimen is required to produce treatment outcomes, which has created a need for portable LED devices. In this study, we aimed to develop a portable therapeutic LED device and investigate its healing effect on excisional wounds in a rat model. The 35 × 35 mm-sized LED device was used on a total of 30 rats with full-thickness wounds that were divided into two groups depending on radiation intensity (11.1 and 22.2 mW/cm2 group). LED irradiation was performed every 24 h for 30 min, over 14 days, in direct contact with the wound. Percentage wound closure was measured by photographic quantification and was assessed histologically using haematoxylin and eosin (H&E) and Masson's Trichrome staining, and immunohistochemistry for Vascular endothelial growth factor (VEGF) and CD31. Percentage wound closure was significantly higher in 22.2 mW/cm2 irradiated wounds than that in the control wounds on days 7 and 10. The area of collagen deposition was remarkably larger in 22.2 mW/cm2 irradiated wounds than that in the control, with more horizontally organized fibres. CD31 immunostaining confirmed a significant increase in the number of microvessels in 22.2 mW/cm2 irradiated wounds than that in the control wounds, although there was no difference in VEGF immunostaining. Our novel portable LED device accelerates wound healing in a rat model, raising the possibility that portable LED devices can combine convenience with accessibility to play an innovative role in wound dressing.

Comparative Study of Small Vessel (under 0.8 mm) Anastomosed Free Flap and Larger Vessel (over 0.8 mm) Anastomosed Free Flap; Does Supermicrosurgery Provide Sufficient Blood Flow to the Free Flap?

BACKGROUND: This study aimed to quantify the blood flow of free flaps and compare the blood flow of small vessel (<0.8 mm) and larger vessel (>0.8 mm) anastomosed free flaps. METHODS: This retrospective study included patients treated successfully with a perforator free flap in the lower extremity between June 2015 and March 2017. A color duplex ultrasound system measured the flow volume through the pedicle by analyzing the mean flow peak velocity, flow volume, and flow volume per 100 g of the flap. RESULTS: A total of 69 patients were enrolled in this study. There was no statistical difference in peak velocity between the small vessel anastomosed free flap (25.2 ± 5.6) and larger vessel anastomosed free flap (26.5 ± 5.4). Flow volume (6.8 ± 4.2 vs. 6.3 ± 3.6) and flow volume/100 g (3.6 ± 3.9 vs. 6.2 ± 6.9) also did not show significant differences. CONCLUSION: Small vessel (<0.8 mm) free flaps showed similar flow velocity and flow volume to larger vessel (>0.8 mm) anastomosed free flaps. Blood flow to the small vessel anastomosed free flap was sufficient despite its small vessel size.

Hybrid Bionic Nerve Interface for Application in Bionic Limbs.

Intuitive and perceptual neuroprosthetic systems require a high degree of neural control and a variety of sensory feedback, but reliable neural interfaces for long-term use that maintain their functionality are limited. Here, a novel hybrid bionic interface is presented, fabricated by integrating a biological interface (regenerative peripheral nerve interface (RPNI)) and a peripheral neural interface to enhance the neural interface performance between a nerve and bionic limbs. This interface utilizes a shape memory polymer buckle that can be easily implanted on a severed nerve and make contact with both the nerve and the muscle graft after RPNI formation. It is demonstrated that this interface can simultaneously record different signal information via the RPNI and the nerve, as well as stimulate them separately, inducing different responses. Furthermore, it is shown that this interface can record naturally evoked signals from a walking rabbit and use them to control a robotic leg. The long-term functionality and biocompatibility of this interface in rabbits are evaluated for up to 29 weeks, confirming its promising potential for enhancing prosthetic control.

Further insight in selecting the ideal vein for lymphaticovenous anastomosis: utilizing the anatomy and Venturi effect of a small vein/venule draining into the main vein.

INTRODUCTION: The functional and dilated lymphatic vessel and veins with minimal backflow and pressure are considered ideal for lymphaticovenous anastomsosis (LVA). However, how to select the ideal vein remains to be determined. This study aims to provide further insight in selecting the ideal vein. MATERIAL AND METHODS: This is a retrospective study evaluating 166 limbs with lymphedema with a minimal follow-up period of 12 months. The surgical approach included side-to-end LVA where one group used a non-Venturi LVA and the other used a small branch draining into a major vein (Venturi LVA). Preoperative, postoperative 1, 3, 6, 12 months limb volume, circumference, reduction volume and ratio were evaluated. RESULTS: The postoperative volume reduction was significant for both groups when compared to their respective preoperative volume. When compared between the 2 groups, the Venturi LVA had a significantly higher reduction volume and ratio at postoperative 1 month (240.82±260.73 cm³ vs 364.27±364.08 cm³, 6.13±5.62% vs 8.77±6.64%; p<0.05) and at 3 months (289.19±291.42 cm³ vs 432.50±395.04cm³, 7.31 ± 6.39% vs 10.55 ± 6.88%; p<0.05) However, the reduction volume and ratio was not significant towards month 6 and 12. CONCLUSION: This study provides further insight in selecting the ideal vein for LVA. By using a small vein draining into the main vein, valves play a role in reducing backflow. Furthermore, the Venturi effect allows significantly enhanced drainage especially in the initial period after surgery. The effect slowly plateaus after few months ultimately having a similar outcome of reduction at 12 months.

The Quality of Life after Lymphaticovenous Anastomosis in 118 Lower Limb Lymphedema Patients.

Background This is a prospective study on 118 patients who underwent lymphaticovenous anastomosis (LVA) due to secondary lower limb lymphedema between January 2018 and October 2020 to evaluate patients' quality of life (QOL) using the Quality of Life Measure for Limb Lymphedema (LYMQoL) questionnaire. Methods The outcome measurement included the LYMQoL leg scoring system tool evaluating the function, appearance, symptom, mood, and overall outcome. In addition, correlation analysis was performed for three factors: based on International Society of Lymphology (ISL) stages, disease duration, and amount of volume reduction. Results The LYMQoL tool overall satisfaction score significantly increased at all intervals from 4.4 ± 0.2 preoperative to 6.5 ± 0.3 postoperative at 12 months ( p < 0.001). Significant findings were seen for each domain scores compared preoperatively and at 12 months: function score (18.6 ± 0.5 to 15.4 ± 0.6), appearance score (17.8 ± 0.5 to 16.0 ± 0.6), symptom score (11.8 ± 0.3 to 8.9 ± 0.4), and mood score (14.5 ± 0.4 to 11.4 ± 0.5; p < 0.05). The correlation analysis between improvement of the overall score and the ISL stage ( p = 0.610, correlation coefficient [ r ] = - 0.047), disease duration ( p = 0.659, r = - 0.041), and amount of limb volume reduction ( p = 0.454, r = - 0.070) showed no statistical significance. Conclusion The QOL of secondary lower limb lymphedema patients was significantly improved after LVA regardless of the severity of disease, duration of disease, and amount of volume reduction after LVA. Understanding the patient-reported outcome measurement will help the surgeons to manage and guide the expectations of the patients.

"Color Contrast" Technique using 10 % Sodium Fluorescein and Blue Marker to Maximize Visualization During Lymphaticovenous Anastomosis.

Lymphatics vessel wall and lumen visualization during anastomosis process is quite challenging for which different techniques were described with variable efficacy. Double opposing color contrast is created using 10% Sodium Fluorescein (FS) which stains lymphatic fluid with yellow causing a clear contrast to blue marker painted lymphatic wall improving the intra-lumen visualization during anastomosis process. This retrospective study evaluated the success rate of performing anastomosis between the side of the lymphatic vessel to the end of the vein (S-to-E LVA) for 281 patients. The LVA assessment showed mean lymphatic diameter of 0.44±0.09mm and mean vein diameter of 0.57±0.14mm with S-to-E success rate of 100% confirmed by post-anastomosis Indocyanine green lymphography. No adverse events were encountered, and FS was not used in two patients due to positive skin allergy test. This method has the advantages of not needing additional device, allows clear visualization and not staining the surrounding structures. This approach using opponent color contrast between fluorescent yellow and blue marker improved vessel edge identification which translated into higher visualization and patency with 100% success rate in S-to-E LVA performance.

The Role of Escin as a Topical Agent for Lymphedema Treatment in a Rat Model.

Escin, a naturally derived material isolated from horse chestnut, is used as an anti-inflammatory and anti-edema agent. This study aimed to evaluate its effects on lymphedema in a rat tail model. We divided the rats into five groups. The treatment groups received topical application of escin gel at concentrations of 20%, 10%, 2%, and 0.5% for 4 weeks. The fifth group served as a control. We performed volumetric (water displacement) tests, H&E staining, and LYVE-1 immunohistochemical staining, followed by statistical evaluation. All treatment groups showed significant volumetric reductions compared with the control group, but no significant differences were observed between the treatment groups. H&E staining showed a significant reduction in dermal thickness in the 20%, 10%, and 2% escin treatment groups compared to the control group. Within the treatment groups, the 2% escin group showed a significant difference compared with the 20% and 10% escin groups (p = 0.021 for both). LYVE-1 immunohistochemical staining revealed a significantly higher mean lymphatic vessel count in the 2% escin group compared with the 20%, 10%, and 0.5% escin-treated groups and the control group (p = 0.019, p = 0.025, p = 0.019, and p = 0.032 respectively). Topical escin applied to a rat tail model of acute lymphedema resulted in a significant reduction in tail volume, reduced dermal thickness, and increased lymphatic structures. The 2% escin concentration may be the optimal dose for improving lymphedema in this model. Further research is warranted to explore the clinical application of escin in patients with lymphedema.

Decompression of Axillary vein - An essential adjunct for advanced lymphedema.

INTRODUCTION: In advanced lymphedema, lymphovenous anastomosis (LVA) can be a solution based on utilizing the pressure gradient between the high pressure lymphatics and low pressure veins. If the vein pressure in high, the effect affect surgery will be less optimal. This study evaluated the effect of axillary vein perivascular scar release on LVA. MATERIALS AND METHODS: This is a retrospective study of 40 upper limb stage 2 and 3 lymphedema patients divided into 2 groups with an average follow-up of 33 months (minimal of at least 12 months); scar-released group (n=25) and control group (n=15). All patients underwent LVA with or without lymph node transfer. Demographic data, outcome (volumetric change and bioimpedence analysis (BIA)), and major veins (axillary, basilic and cephalic) diameter changes were evaluated. RESULTS: Both groups showed significant reduction in volume and BIA parameters after LVA. The scar-released groups (24/25 with lymph node transfer and 1 without) showed statistically higher reduction of BIA analysis compared to the control group at 1, 6 and 12 months after LVA. The changes in the major veins after axilla scar release showed significant changes in all 3 veins. There was a significant correlation between cephailic vein dimeter reduction and BIA measurement. CONCLUSION: The release of perivascular scar in the axially vein may result in better outcome after LVA. This is based on the finding that scar release shows correlation between cephailic vein dimeter reduction and BIA measurement suggesting reduction of venous pressure in the peripheral vein increasing the pressure gradient between the lymphatic and venous system allowing better outflow after LVA.