Evaluating the Surgical Outcome of Lymphovenous Anastomosis in Breast Cancer-Related Lymphedema Using Tc-99m Phytate Lymphoscintigraphy: Preliminary Results.

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.

Immediate inguinal lymphaticovenous anastomosis following lymphadenectomy in skin cancer of lower extremities.

BACKGROUND: Secondary lymphedema following inguinal lymph node dissection in lower extremities skin cancer reduce the patients' quality of life. Immediate lymphaticovenous anastomosis (LVA) at groin is a procedure intended to prevent secondary lymphedema. The data regarding the long-term efficacy and safety of this procedure was limited. Therefore, we evaluated the long-term outcomes of immediate LVA in patients with melanoma and non-melanoma skin cancer of the lower extremities. METHODS: The retrospective data review of patients with melanoma or squamous cell carcinoma of the lower extremities underwent oncologic tumor resection with groin node dissection between December 2013 and December 2016 was performed. Seven patients underwent immediate LVA (intervention) at groin after node dissection and 22 acted as controls. The occurrence of lymphedema and oncologic outcomes were followed up to 7 years. RESULTS: Fifteen patients (51.7%) developed postoperative lymphedema, which were three patients in the intervention group and twelve patients in the control group (p = 0.68). The intervention group had significant lower 2-year (57.1% versus 77.3%) and 5-year overall survival (14.3% versus 54.5%) (p = 0.035). The intervention group had reduced 2-year (28.6% versus 86.4%) and 5-year (28.6% versus 68.2%) Recurrence Free Survival (RFS) (p = 0.013). The intervention group also had reduced 2-year (0% versus 90%) and 5-year (0% versus 70%) Metastasis Free Survival (MFS) (p = 0.003). CONCLUSION: Immediate inguinal LVA following groin node dissection in lower extremity skin cancer patients did not reduce the incidence of lymphedema. Unfortunately, it was associated with lower overall survival and an increase in tumor recurrence and metastasis.

Lymphatic Tissue Transfer: Ultrasound-Guided Description and Preoperative Planning of Vascularised Lymph Nodes, Lymphatic Units, and Lymphatic Vessels Transfers.

BACKGROUND: The modern concept of lymphatic transfer includes vascularised lymph node transfer (VLNT), lymphatic vessels transfer (lymph interpositional flap transfer, LIFT) and lymphatic system transfer (vascularised lymph nodes and afferent lymphatics, LYST). The aim of this paper was to report our experience with different types of lymphatic transfer. PATIENTS AND METHOD: From June 2016 to June 2020, 30 consecutive patients affected by extremity lymphedema and 15 patients affected by post-traumatic lower extremity soft tissue defects, underwent lymphatic transfer (VLNT, LYST or LIFT). All cases were preoperatively evaluated by both high frequency and ultra-high frequency ultrasound. Flap features were recorded, as well as qualitative and quantitative outcomes at 1 year postoperative. RESULTS: The mean postoperative lymphedema index reduction was 7.2 ± 5.7 for upper extremity and 20.7 ± 7.1 for lower extremity. No dismission of compression garments occurred, 12 patients (26%) referred more stable results of physical treatment and 1 case showed a 1-class compression reduction. All the LIFTs aimed as preventive did not develop post-traumatic lymphedema. In all cases of distal placement of VLNT and/or LYST, patients were dissatisfied with the aesthetic appearance of reconstruction, while no donor site scar disappointment was referred. CONCLUSION: When LVA is not feasible, LTT may represent a valid treatment option. This report was aimed at comprehensively describing and assessing how different lymphatic tissue transfer modalities may fulfil the different reconstructive needs of lymphedema patients.

Impact of retrograde anastomosis during supermicrosurgical lymphaticovenous anastomosis for cancer-related lower limb lymphedema: A retrospective cohort propensity-score-matched outcome analysis.

BACKGROUND: In addition to antegrade anastomosis, retrograde anastomosis has been thought to offer further improvements after lymphaticovenous anastomosis (LVA) by bypassing the retrograde lymphatic flow. However, this concept has yet to be validated. The aim of this study was to determine the impacts on outcomes of performing both retrograde and antegrade anastomosis, as compared to antegrade-only anastomosis for treating lower limb lymphedema. STUDY DESIGN: This was a retrospective cohort propensity score-matched study. Eighty-seven patients with gynecologic cancer-related lower limb lymphedema were enrolled, including 58 patients who had received both antegrade and retrograde anastomoses (Group I) and 29 patients who had received antegrade-only anastomoses (Group II) as the control group. LVA was the primary treatment. Patients who had previous LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, and functional parameters including the ratio of indocyanine green-enhanced and flow-positive lymphatic vessels were recorded. Magnetic resonance volumetry was used for outcome assessments. The primary endpoint was the volume change at 6 months after LVA. RESULTS: After matching, a total of 26 patients have remained in each group. All parameters were matched except that Group I still had significantly more median LVA performed compared to Group II (8 [IQR: 5.3-10.0] vs. 5.5 [4.3-6.0], p = 0.001, respectively). Group II showed more post-LVA improvements at six-month and one-year follow-up compared to Group I but without statistically significant differences. CONCLUSION: The use of supplementary retrograde anastomoses is discouraged since it may lead to inferior post-LVA outcome compared to antegrade-only anastomoses.

Lymphaticovenular Anastomosis for Advanced-Stage Peripheral Lymphedema: Expanding Indication and Introducing the Hand/Foot Sign.

BACKGROUND: Effective lymphaticovenular anastomosis (LVA) requires identification of functioning lymphatics, which are not always visible with contrast-based imaging in advanced-stage lymphedema patients. Ultrasound (US) allows to identify preoperatively functioning lymphatic vessels even in limbs severely affected by lymphedema. Moreover, in our experience, we observed an interesting clinical sentry in advanced-stage lymphedema patients, the hand/foot sign that is analyzed in this paper. PATIENTS AND METHODS: From January 2016 to January 2019, 76 consecutive advanced-stage secondary lymphedema patients underwent LVA. Preoperative planning included lymphoscintigraphy, indocyanine-green lymphography (ICG-L) and US. Patients' features, the hand/foot sign (preservation of more normal skin on the dorsum of the hand or foot), lymphatic degeneration, quantitative, qualitative, and composite outcomes at 1-year follow-up were evaluated. RESULTS: An average number of 3±0.1 LVA was performed in upper limb lymphedema (ULL) (range 2-5, 47 patients) and of 4±1.08 LVAs in lower limb lymphedema (LLL) cases (range 4-7, 29 patients). The composite outcome was positive in 45 cases (59.7%). The "negative" hand /foot sign was significantly associated with presence of functioning lymphatic channels. The incidence of adverse outcomes was significantly higher in patients with positive hand/foot sign. CONCLUSION: Patients with no functioning lymphatic vessels detectable by lymphoscintigraphy and ICG-L may still have functioning lymphatic channels that can be identified preoperatively by ultra-high-frequency ultrasound and salvaged by LVA. The "hand/foot sign" is a simple clinical sentry that appears to be correlated with higher probability of being able to localize functional lymphatics for potential lymphovenous bypass surgery.

Additional Lymphaticovenular Anastomosis on the Posterior Side for Treatment of Primary Lower Extremity Lymphedema.

The efficacy of lymphaticovenular anastomosis (LVA) for the treatment of primary lymphedema has been reported. Previous research suggested the efficacy of LVA on the anterior side of the lower limb, but no research has yet underlined the effectiveness of LVA on the posterior side. In the present study, we aimed to investigate the efficacy of LVA on the posterior side of the lower leg for treatment of primary lymphedema, i.e., whether further improvement of primary lower extremity lymphedema could be expected by performing LVA on the posterior side of the lower limb in addition to the LVA on the anterior side, which is usually performed. Forty-five patients with primary lower extremity lymphedema who underwent LVA twice between March 2018 and September 2020 were retrospectively investigated. Patients were classified into two groups: those who underwent LVA on the posterior side in the second operation (PoLVA group) and those who underwent LVA on the medial and anterior sides again in the second operation (MeLVA group). All patients underwent LVA on the medial and anterior sides in the first operation, but no sufficient improvement was observed. The following factors in the second operation were compared between the two groups: skin incision length, the number of anastomoses, the diameters of the lymphatic vessels, the time required for the dissection of the lymphatic vessels and veins and the reduction in volume. LVA resulted in 227 anastomoses (106 anastomoses in the PoLVA group and 121 anastomoses in the MeLVA group) in 26 patients with primary lymphedema of the lower extremities in two surgeries. The reduction in lower extremity lymphedema index was significantly greater in the PoLVA group than that in the MeLVA group (10.5 ± 4.5 vs. 5.5 ± 3.6; p = 0.008), and the number of anastomoses in the PoLVA group was significantly lower than that in the MeLVA group (3.5 ± 0.6 vs. 4.6 ± 1.0; p = 0.038). LVA on the posterior side subsequent to LVA on the medial and anterior sides resulted in the further improvement of primary lower extremity lymphedema with fewer numbers of anastomoses.

Superficial Circumflex Iliac Artery Perforator Flap Elevation Using Preoperative High-Resolution Ultrasonography for Vessel Mapping and Flap Design.

BACKGROUND: The superficial circumflex iliac artery (SCIA) perforator (SCIP) flap has gained acceptance among reconstructive microsurgeons, the minimal donor site morbidity being its greatest advantage. The purpose of this article is to introduce the use of preoperative ultrasonography to facilitate elevation and to avoid postoperative complications of the SCIP flap. METHODS: Preoperative mapping of the SCIA and the superficial circumflex iliac vein (SCIV) using a high-resolution ultrasound system were performed in patients undergoing reconstruction using a free SCIP flap. The skin paddle was designed placing the SCIA and the SCIV in the middle of the flap. RESULTS: Preoperatively marked SCIA and SCIV were found intraoperatively in all cases. The skin paddle design for sufficient arterial inflow and venous drainage resulted in no postoperative flap complications. CONCLUSION: The use of a preoperative high-resolution ultrasound system significantly facilitates elevation of the SCIP flap, notably via the following 2 points: 1) pedicle can always be found under the markings made with preoperative ultrasonography, 2) satisfactory perfusion of the flap can be guaranteed via a safe flap design that includes preoperatively marked vessels within the skin paddle.

Recipient Venule Selection and Anastomosis Configuration for Lymphaticovenular Anastomosis in Extremity Lymphedema: Algorithm Based on 1,000 Lymphaticovenular Anastomosis.

BACKGROUND: The lymphaticovenular anastomosis (LVA) has three components, lymphatics, venules, and anastomosis, and all of them influence the anastomotic pressure gradient. Although it has been demonstrated that venule flow dynamics has an independent impact on the outcomes regardless the degeneration status of lymphatic vessels, recipient venules (RV) have been mainly neglected in literature. METHODS: From January 2016 to February 2020, 232 nonconsecutive patients affected by extremity lymphedema underwent LVA, for a total of 1,000 LVAs. Only patients with normal-to-ectasic lymphatic collectors were included to focus the evaluation on the RV only. The preoperative collected data included the location, diameter, and continence of the selected venules, the expected number, the anastomoses configuration, and their flow dynamics according to BSO classification. RESULTS: The 232 patients included 117 upper limb lymphedema (ULL) and 115 lower limb lymphedema (LLL). The average size of RV was 0.81 ± 0.32 mm in end-to-end (E-E), 114 ± 0.17 mm in end-to-side (E-S), 0.39 ± 0.22 mm in side-to-end (S-E), and 0.76 ± 0.38 mm in side-to-side (S-S) anastomoses. According to the BSO classification, on a total of 732 RV, 105(14%) were backflow venules, 136 (19%) were slack, and 491 (67%) were outlet venules. Also, 824 (82%) were E-E, 107 (11%) were E-S, 51 (5%) were S-E, and 18 (2%) were S-S anastomoses. CONCLUSION: Based on 1,000 LVAs with similar lymphatic characteristics, we propose our algorithm that may aid the lymphatic microsurgeon in the selection of RV and the consequent anastomosis configuration, in order of obtain the best flow dynamic through the LVA. This therapeutic study reflects level of evidence IV.

Selection of Optimal Functional Lymphatic Vessel Cutoff Size in Supermicrosurgical Lymphaticovenous Anastomosis in Lower Extremity Lymphedema.

BACKGROUND: Functional lymphatic vessels are essential for supermicrosurgical lymphaticovenous anastomosis. Theoretically, the larger the lymphatic vessel, the better the flow. However, large lymphatic vessels are not readily available. Since the introduction of lymphaticovenous anastomosis, no guidelines have been set as to how small a lymphatic vessel is still worthwhile for anastomosis. METHODS: In this longitudinal cohort study, unilateral lower limb lymphedema patients who underwent lymphaticovenous anastomosis between March of 2016 and January of 2019 were included. Demographic data and intraoperative findings including the number and size of lymphatic vessels were recorded. The cutoff size was determined by receiver operating characteristic curve analysis, based on the functional properties of lymphatic vessels. Clinical correlation was made with post-lymphaticovenous anastomosis volume measured by magnetic resonance volumetry. RESULTS: A total of 141 consecutive patients (124 women and 17 men) with a median age of 60.0 years (range, 56.7 to 61.2 years) were included. The cutoff size for a functional lymphatic vessel was determined to be 0.50 mm (i.e., lymphatic vessel0.5) from a total of 1048 lymphatic vessels. Significant differences were found between the number of lymphatic vessels0.5 anastomosed (zero to one, two to three, and greater than over equal to four lymphatic vessels0.5), the median post-lymphaticovenous anastomosis volume reduction (in milliliters) (p < 0.001), and the median percentage volume reduction (p = 0.012). CONCLUSIONS: Lymphatic vessel0.5 can be a valuable reference for lymphaticovenous anastomosis. Post-lymphaticovenous anastomosis outcome can be enhanced with the use of lymphatic vessel0.5 for anastomoses. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Recent Advances in Ultrasound Technology: Ultra-High Frequency Ultrasound for Reconstructive Supermicrosurgery.

BACKGROUND: Currently, microsurgeons are in the era of supermicrosurgery and perforator flap reconstruction. As these reconstructions frequently utilize vessels that are smaller than a single millimeter, understanding of location of lymphatic vessels and perforator anatomy preoperatively is essential. To change with the times, the role of ultrasound has changed from just an adjunct to primary imaging of the choice in reconstructive supermicrosurgery. Recently, a novel ultrasonographic technique involving the use of ultra-high frequency ultrasound (UHFUS) frequencies has entered the scene, and appears a promising tool in surgical planning. METHODS: The literatures on the applications of UHFUS in reconstructive supermicrosurgery were retrieved and reviewed from more than 60 literatures have been published on the surgical applications of UHFUS. RESULTS: Nine studies were retrieved from the literature on the applications of UHFUS in reconstructive supermicrosurgery. The articles report both application for lymphatic surgery and perforator flaps. CONCLUSION: UHFUS application involves an increasing number of reconstructive supermicrosurgery field. UHFUS is a valuable and powerful tool for any reconstructive surgeons who are interested in performing supermicrosurgery.

Designing An Anterolateral Thigh Flap Using Ultrasound.

BACKGROUND: Preoperative knowledge of themicrovascular anatomy of a patientmay improve safetyand efficacy and reduce morbidity. Today, with the advancement in technology, ultrasound can provide minute details of the structures within the body, which makes this technology very helpful in preoperative evaluation of the traditional perforator flaps as well as thin, superthin, and pure skin perforator flaps. METHODS: In this article, we will describe the design of one of the most popular perforator flaps, the anterolateral thigh (ALT) flap, using high-frequency and ultrahigh-frequency ultrasound technology. RESULTS: Ultrasound technology allows to study preoperatively the ALT donor-site and its microvascular anatomy by using different US modalities in order to provide a virtual surgical plan to the operating surgeon. CONCLUSION: Ultrasound technology allow to expand preoperative knowledge of flap microvascular anatomy and its course within the subcutaneous tissue up to and within the dermis, allowing to select the best perforator for the given reconstruction and the plane of elevation for thin, superthin and pure skin perforator flap.

Breast cancer related upper limb lymphedema: approach and surgical management.

Lymphedema of the upper extremities in a common, chronic, progressive and debilitating disease, that affects the increasing population of cancer survivors. The gold standard is nowadays an integrated approach, including conservative and surgical treatment. Lymphatic surgery, particularly the physiologic procedures including lymphatic-venous anastomosis and vascularized lymph node transfer, should be offered to lymphedema patients as soon as possible, aimed to ameliorate the subjective symptoms and to interrupt the degeneration cascade that makes this condition progressive over time. Indications for surgery, patient selection, and diagnostic tools will be discussed.

Lower Limb Lymphedema Patients Can Still Benefit from Supermicrosurgical Lymphaticovenous Anastomosis (LVA) after Vascularized Lymph Node Flap Transfer (VLNT) as Delayed Lymphatic Reconstruction-A Retrospective Cohort Study.

BACKGROUND: For lymphedema patients who received a vascularized lymph node flap transfer (VLNT) as their primary treatment, what are the treatment options when they seek further improvement? With recent publications supporting the use of lymphaticovenous anastomosis (LVA) for treating severe lymphedema, we examined whether LVA could benefit post-VLNT patients seeking further improvement. METHODS: This retrospective cohort study enrolled eight lymphedema patients with nine lymphedematous limbs (one patient suffered from bilateral lower limb lymphedema) who had received VLNT as their primary surgery. Patients with previous LVA, liposuction, excisional therapy, or incomplete data were excluded. LVA was performed on nine lower lymphedematous limbs. Demographic data and intraoperative findings were recorded. Preoperative and postoperative limb volumes were measured with magnetic resonance volumetry. The primary outcome was the limb volume measured 6 months post-LVA. RESULTS: The median duration of lymphedema before LVA was 10.5 (4.9-15.3) years. The median waiting time between VLNT and LVA was 41.4 (22.3-97.9) months. The median volume gained in the lymphedematous limb was 3836 (2505-4584) milliliters (mL). The median post-LVA follow-up period was 18 (6-30) months. Significant 6-month and 1-year post-LVA percentage volume reductions were found compared to pre-LVA volume (both p < 0.001). CONCLUSION: Based on the results from this study, the authors recommend the use of LVA as a secondary procedure for post-VLNT patients seeking further improvement.

Use of Preoperative High-Resolution Ultrasound System to Facilitate Elevation of the Superficial Circumflex Iliac Artery Perforator Flap.

BACKGROUND: During elevation of the superficial circumflex iliac artery (SCIA) perforator (SCIP) flaps, the flap pedicle must often be converted from the superficial branch to the deep branch of the SCIA, complicating and prolonging the procedure. The goal of the present study was to demonstrate the effectiveness of high-resolution ultrasonography to decrease the conversion rate on which no previous report has focused, by making a comparison with a conventional method. METHODS: Forty-five consecutive cases where free SCIP flap transfer was performed for reconstruction were retrospectively reviewed. To preoperatively mark the course of the superficial branch, handheld Doppler ultrasonography was used in 27 cases (group 1) and a high-resolution ultrasound system in 18 cases (group 2). RESULTS: The conversion rate was significantly greater in group 1 than in group 2 (10/27 [37%] vs. 0/18 [0%], p = 0.003]. The frequency of use of multiple venous anastomoses was significantly higher in group 1 than in group 2 (21/27 [78%] vs. 2/18 [11%], p < 0.001). The operative time was significantly longer in group 1 than in group 2 (p = 0.038). There were no significant differences in postoperative complication rates (1/27 [4%] versus 0/18 [0%], p = 1.0). CONCLUSION: The use of a preoperative high-resolution ultrasound system significantly decreased the rate from of intraoperative conversion from the superficial branch to the deep branch of the SCIA. It also resulted in significantly fewer venous anastomoses and a shorter operative time, while maintaining a low incidence of postoperative complications.

Intraoperative Real-Time Visualization of the Lymphatic Vessels Using Microscope-Integrated Laser Tomography.

BACKGROUND: Detection and selection of the lymphatic vessels are important for maximizing therapeutic efficacy of lymphaticovenular anastomosis (LVA). Some imaging modalities have been reported to be useful for intraoperative identification of the lymphatic vessels, but they have limitations. In this article, we present new capabilities of intraoperative laser tomography, which was used to evaluate the lumen of the lymphatic vessel and to validate the patency of anastomosis. METHODS: Fifty-two patients with upper extremity lymphedema secondary to breast cancer treatment underwent indocyanine green (ICG) lymphography and real-time laser tomography imaging of ICG-enhanced lymphatic vessels intraoperatively before transecting the vessels during LVA. The imaging findings of the lymphatic vessels in laser tomography were investigated. Time required for scanning of the lymphatic vessels was compared between laser tomography and ultrasonography. The correlation between the thickness of the lymphatic vessel wall measured with laser tomographic imaging and the histologically measured thickness of the lymphatic vessel wall was examined. The patency of anastomosis sites was determined based on the image using laser tomography immediately after establishment of LVA. RESULTS: A total of 132 ICG-enhanced lymphatic vessels were scanned with laser tomography showing clear lumen with surrounding vessel wall. The required time for lymphatic vessel scanning was significantly shorter with laser tomography than with ultrasonography (1.6 ± 0.3 vs. 4.8 ± 1.2 minutes; p = 0.016). Strong correlation was seen between the thickness of the lymphatic vessels wall measured using laser tomography and the histologically measured thickness of the lymphatic vessel wall (r = 0.977, 95% confidence interval: 0.897-0.992, p < 0.001). The quality of patency was evaluated immediately after anastomosis, which assisted in deciding whether reanastomosis was needed. CONCLUSION: Microscope-integrated laser tomography provides real-time images of the lymphatic vessels in extremely high resolution and enables evaluation of lymphatic lumen condition and objective post-LVA anastomosis status.