RESUMEN
Early postoperative wound complications in revascularization procedures in the groin very often include complications associated with injury to the lymphatic system such as lymphocele and lymphorrhea with subsequent local infectious complications and the risk of infection of prosthetic grafts. We present a case report of successful treatment of postoperative lymphocele with subsequent lymphatic fistula and dehiscence of the surgical wound by intranodal embolization of the injured lymph node with Histoacryl tissue glue.
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Embolización Terapéutica , Ingle , Linfocele , Humanos , Linfocele/etiología , Linfocele/terapia , Embolización Terapéutica/métodos , Masculino , Enbucrilato/uso terapéutico , Ganglios Linfáticos/trasplante , Persona de Mediana Edad , Complicaciones Posoperatorias/terapia , Adhesivos Tisulares/uso terapéutico , AncianoRESUMEN
BACKGROUND: Vascularized lymph node transfer (VLNT) involves the microvascular transplantation of functional lymph nodes from a donor site into a limb affected by lymphedema to restore the normal flow of lymphatic fluid. Despite the increasing clinical experience with VLNT, there remains insufficient data to support its routine use in clinical practice. Here, we aim to evaluate the effectiveness and safety of VLNTs for upper limb lymphedema and compare clinical outcomes when using different donor sites. METHODS: We carried out a systematic search of the literature through PubMed and Scopus databases for studies on VLNT for upper limb lymphedema. Primary and secondary outcomes included circumference reduction rate (CRR) and infection reduction rate by postoperative cellulitis episodes for the efficacy and safety of VLNT. Pooled analysis was performed using the inverse variance weighting meta-analysis of single means using the meta package in R software. Subgroup analyses were performed for donor and recipient sites, age groups, follow-ups, and symptom durations. Quality assessment was performed using the Newcastle-Ottawa Scale for nonrandomized studies. RESULTS: A total of 1089 studies were retrieved from the literature, and 15 studies with 448 upper limb lymphedema patients who underwent VLNT were included after eligibility assessment. The mean CRR was 34.6 (18.8) and the mean postoperative cellulitis episodes per year was 0.71 (0.7). The pooled analysis of CRR was 28.4% (95% confidence interval, 19.7-41.1) and postoperative cellulitis episodes showed a mean of 0.59 (95% confidence interval, 0.36-0.95) using the random-effect model. Subgroup analyses showed significant group differences in recipient site for CRR and postoperative cellulitis episodes with the wrist comprising the highest weights, and patients younger than 50 years showing a lower postoperative infection. CONCLUSIONS: Vascularized lymph node transfer using gastroepiploic flaps at the wrists has shown a significant difference in reductions of limb circumference and cellulitis episodes in upper limb lymphedema patients when compared with other donor sites. However, further prospective studies are needed to consolidate this finding.
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Ganglios Linfáticos , Linfedema , Extremidad Superior , Humanos , Linfedema/cirugía , Extremidad Superior/cirugía , Ganglios Linfáticos/trasplante , Ganglios Linfáticos/irrigación sanguínea , Sitio Donante de Trasplante , Resultado del TratamientoRESUMEN
Background: As an increased number of women beat breast cancer worldwide, the breast cancer related lymphedema has gained more attention recently. The vascularized omentum lymph node transfer has been approached as an useful tool for advanced and recurrent cases. The purpose of the paper is to emphasize the advantages and disadvantages of this method. Materials and Methods: This retrospective study consists of 17 patients known with breast cancer related lymphedema who received vascularized omentum lymph node transfer. Data was recorded between January 2022 and January 2023. Patients diagnosed with secondary lymphedema stage II or III, unresponsive to previous microsurgical lymphovenous bypass were included. Results: The most prevalent affected site was the left upper limb (59%), where edema was mainly identified in the forearm (75%). Nevertheless, more than half of the subjects have previously received lymphaticovenous anastomosis. The correlation between the stage of lymphedema and the postoperative reduction of the volume of the affected limb was -0.26, the slope to reached -0.33, with an intercept value of 2.64. The follow-up period showed reduced upper limb volume and an improved quality of life. Conclusion: Through an experienced hand, this versatile flap brings hope to breast cancer survivors with lymphedema.
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Linfedema del Cáncer de Mama , Neoplasias de la Mama , Ganglios Linfáticos , Epiplón , Calidad de Vida , Humanos , Femenino , Estudios Retrospectivos , Resultado del Tratamiento , Persona de Mediana Edad , Ganglios Linfáticos/trasplante , Epiplón/trasplante , Linfedema del Cáncer de Mama/cirugía , Linfedema del Cáncer de Mama/etiología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/patología , Anciano , Colgajos Quirúrgicos , Adulto , Linfedema/cirugía , Linfedema/etiología , Estudios de SeguimientoRESUMEN
Hydrocephalus is routinely treated with ventriculoperitoneal shunt drainage of cerebrospinal fluid (CSF), a procedure plagued by high morbidity and frequent revisions. Vascularized submental lymph node (VSLN) transplants act as lymphatic pumps to drain interstitial fluid (ISF) from lymphedematous extremities. As the field of neuro-lymphatics comes to fruition, we hypothesize the efficacy of VSLN in the drainage of intracranial CSF-ISF. We report novel placement of VSLN in the temporal subdural space in two patients diagnosed with symptomatic communicating hydrocephalus. At a minimum follow-up of 1 month postoperatively, both experienced radiological and clinical improvements.
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Hidrocefalia , Linfedema , Humanos , Hidrocefalia/cirugía , Ganglios Linfáticos/trasplante , Linfedema/cirugía , Extremidades , CuelloRESUMEN
Objective: To summarize the research progress of combined surgical treatment of lymphedema based on vascularized lymph node transfer (VLNT), and to provide systematic information for combined surgical treatment of lymphedema. Methods: Literature on VLNT in recent years was extensively reviewed, and the history, treatment mechanism, and clinical application of VLNT were summarized, with emphasis on the research progress of VLNT combined with other surgical methods. Results: VLNT is a physiological operation to restore lymphatic drainage. Multiple lymph node donor sites have been developed clinically, and two hypotheses have been proposed to explain its mechanism for the treatment of lymphedema. But it has some inadequacies such as slow effect and limb volume reduction rate less than 60%. To address these inadequacies, VLNT combined with other surgical methods for lymphedema has become a trend. VLNT can be used in combination with lymphovenous anastomosis (LVA), liposuction, debulking operation, breast reconstruction, and tissue engineered material, which have been shown to reduce the volume of affected limbs, reduce the incidence of cellulitis, and improve patients' quality of life. Conclusion: Current evidence shows that VLNT is safe and feasible in combination with LVA, liposuction, debulking operation, breast reconstruction, and tissue engineered material. However, many issues need to be solved, including the sequence of two surgeries, the interval between two surgeries, and the effectiveness compared with surgery alone. Rigorous standardized clinical studies need to be designed to confirm the efficacy of VLNT alone or in combination, and to further discuss the subsistent issues in the use of combination therapy.
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Ganglios Linfáticos , Linfedema , Humanos , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Ganglios Linfáticos/irrigación sanguínea , Ganglios Linfáticos/trasplante , Vasos Linfáticos/cirugía , Vasos Linfáticos/trasplante , Linfedema/cirugía , Calidad de VidaRESUMEN
BACKGROUND: In this study, the method that can be followed to ensure rapid and uncomplicated recovery of lymph node flap (LNF) applied in the medial of the ankle for lymphedema treatment was investigated. METHODS: Thirty-seven patients with class II of lower limb lymphedema underwent transfer of gastroepiploic LNF to the medial ankle and popliteal fossa areas. At the popliteal fossa region, the wound could always be closed primarily by the advancement of neighboring skin. The wound closure could be classified into three types at the medial ankle area (A) The partially exposed LNF was covered with a split-thickness skin graft (STSG) (n = 9). (B) A larger local flap was elevated, and the donor site of the local flap was covered with STSG (n = 18). (C) The skin flap's donor site was treated with pre-tie sutures (n = 10). RESULTS: In the popliteal region, there was no complication of wound healing. In the ankle region, the wound was coated by a thin layer of hematoma over the exposed LNF in 5 patients of group A. It healed secondarily except for one patient who needed a secondary skin graft. The healing was perfect in group B. In group C the healing was good, but there was a hypertrophic scar in 7 patients and required steroid injection later. CONCLUSION: To avoid complications of the gastroepiploic LNF at the medial ankle, it should be entirely covered by an anteriorly-based local flap, and the donor site defect of the local flap can be treated with either pre-tie sutures or a skin graft.
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Linfedema , Colgajos Quirúrgicos , Humanos , Extremidad Inferior/cirugía , Trasplante de Piel , Ganglios Linfáticos/trasplante , Linfedema/cirugía , Resultado del TratamientoRESUMEN
El linfedema es una enfermedad crónica con una elevada incidencia en nuestra sociedad. En este trabajo presentamos una revisión bibliográfica con los últimos avances en técnicas de imagen y tratamiento quirúrgico con técnicas reconstructivas del linfedema (anastomosis linfático-venosas, trasplante vascularizado de ganglios linfáticos y cirugía profiláctica del linfedema). Además, se establece un protocolo basado en el trabajo de un equipo multidisciplinar (compuesto por rehabilitadores, cirujanos plásticos, radiólogos y médicos nucleares) que optimiza el tratamiento de estos pacientes.(AU)
Lymphedema is a chronic disease with a high incidence in our society. In this paper, we present a review with the latest advances in imaging techniques and surgical reconstructive treatment of lymphedema (lymphovenous anastomosis, vascularized lymph node transfer, and prophylactic lymphedema surgery). In addition, a protocol is established based on a multidisciplinary team (composed of physiatrists, plastic surgeons, radiologists and nuclear medicine radiologists) to optimize the treatment of these patients.(AU)
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Investigación Interdisciplinaria , Linfedema , Microcirugia , Linfedema/complicaciones , Linfedema/diagnóstico , Enfermedad Crónica , Ganglios Linfáticos/trasplante , Linfedema/cirugía , Drenaje Linfático Manual , Rehabilitación , Bases de Datos Bibliográficas , Manejo del DolorRESUMEN
BACKGROUND: Lymph node transfer has been known as a physiologic approach for "curing" lymphedema. The transplantation of methylene blue and carbon nanoparticles stained lymph nodes aims to investigate their impact on the survival of transplanted lymph nodes. METHODS: Four weeks after transplantation, the survival condition of transplanted lymph nodes was detected by the reconnection with lymphatics, reconnected lymphatic function, HE staining, and distribution of B-cells and T-cells. Also, the number of lymphatics (LYVE-1) and blood vessels (CD31) of transplanted lymph nodes was investigated. RESULTS: Reconnected lymphatic function, the number of transplanted lymph nodes of achieving lymphatic reconstruction, and the surviving and potentially surviving ones were close. Besides, the control group (n = 11, CD31: mean = 9.527 ± 1.017, LYVE-1: mean = 21.45 ± 1.780), the methylene blue group (n = 12, CD31: mean = 9.73 ± 0.8998, LYVE-1: mean = 20.67 ± 1.601) and the carbon nanoparticles group (n = 11, CD31:mean = 8.709 ± 1.435, LYVE-1: mean = 19.60 ± 2.268). After calculation, both CD31 and LYVE-1 showed no significant difference statistically among the three groups. CONCLUSIONS: Our findings justify the use of methylene blue and carbon nanoparticles in reverse lymphatic mapping, as they can increase the efficiency of collecting "target lymph nodes" and minimize the iatrogenic injury in the donor area while having no significant adverse effects on the survival condition of transplanted lymph nodes. And this approach is easy to operate and worthy of clinical application and popularization.
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Azul de Metileno , Nanopartículas , Animales , Carbono/uso terapéutico , Modelos Animales de Enfermedad , Enfermedad Iatrogénica , Ganglios Linfáticos/patología , Ganglios Linfáticos/fisiología , Ganglios Linfáticos/trasplante , Azul de Metileno/uso terapéutico , Ratones , Nanopartículas/uso terapéuticoRESUMEN
SUMMARY: Vascularized lymph node transplantation is a surgical approach for the treatment of chronic lymphedema. However, there is no clinical standard for flap placement nor vascular anastomoses. The authors propose a novel flowthrough configuration for an omental vascularized lymph node transplant in the popliteal space. To prepare the popliteal space for an omental free flap, the medial popliteal fat pad and medial head of the gastrocnemius muscle were debulked. Venous anastomoses were completed with vein couplers, joining the right gastroepiploic vein to the medial sural venae comitantes and the left gastroepiploic vein to the lesser saphenous vein. Arterial anastomoses were hand sewn, joining the right gastroepiploic artery to the proximal medial sural artery and the left gastroepiploic artery to the distal medial sural artery, to create the flowthrough configuration. A retrospective review of patients who underwent this procedure at a single institution was performed. Six patients with chronic lymphedema of the lower extremity underwent vascularized lymph node transplantation from June of 2019 to November of 2020. Five patients underwent at least 3 months of postoperative surveillance, with no postoperative complications reported. In this technique contribution, the authors describe a novel flowthrough configuration for an omental free flap to the popliteal space. The popliteal space offers an aesthetically favorable recipient location when appropriately prepared. The medial sural vessels are ideal recipient vessels for the flowthrough omental flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
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Colgajos Tisulares Libres/trasplante , Extremidad Inferior/cirugía , Ganglios Linfáticos/trasplante , Linfedema/cirugía , Epiplón/trasplante , Procedimientos de Cirugía Plástica/métodos , Anciano , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Colgajos Tisulares Libres/irrigación sanguínea , Humanos , Ganglios Linfáticos/irrigación sanguínea , Masculino , Persona de Mediana Edad , Epiplón/irrigación sanguínea , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: This study evaluates clinical outcomes of vascularized lymph node transplantation (VLNT) from the lateral thoracic region and technical modifications. METHODS: Consecutive patients that underwent lateral thoracic VLNT to treat extremity lymphedema were included. Demographic and treatment data were recorded, and outcomes data including limb volume, LDex score, and Lymphedema Life Impact Scale (LLIS), QuickDASH, and LEFS questionnaires, were collected prospectively. Consecutive patients that underwent single-photon emission computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (RLM) were analyzed to characterize the physiological drainage of the normal upper extremity. RESULTS: A consecutive series of 32 flaps were included. At 24 months postoperatively mean reduction in limb volume excess was 47.2% (±11.6; p = 0.0085), LDex score was 63.1% (±8.5; p < 0.001), and LLIS score was 65.1% (±7.4; p < 0.001). Preoperatively 14/31 patients (45.2%) reported cellulitis, and postoperatively there were no episodes at up to 24 months (p < 0.001). No patient developed donor extremity lymphedema at mean 18.6 (±8.3) months follow-up. SPECT/CT-RLM of 182 normal axillae demonstrated that the sentinel lymph node(s) of the upper extremity was consistently anatomically located in the upper outer quadrant of the axilla (97%). CONCLUSIONS: VLNT from the lateral thoracic region is effective and versatile for the treatment of lymphedema with a low donor site complication rate.
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Ganglios Linfáticos/irrigación sanguínea , Ganglios Linfáticos/trasplante , Linfedema/prevención & control , Neoplasias/cirugía , Procedimientos de Cirugía Plástica/métodos , Procedimientos Quirúrgicos Operativos/efectos adversos , Tórax/trasplante , Femenino , Estudios de Seguimiento , Humanos , Linfedema/etiología , Linfedema/patología , Masculino , Persona de Mediana Edad , Neoplasias/patología , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Secondary lymphedema is a leading sequela of cancer surgery and radiotherapy. The microsurgical transfer of lymph node flaps (LNFs) to affected limbs can improve the symptoms. The intra-abdominal cavity contains an abundant heterogenic source. The aim of this study is to aid selection among intra-abdominal LNFs. METHODS: Eight LNFs were harvested in a microsurgical fashion at five sites in 16 cadavers: gastroepiploic, jejunal, ileal, ileocolic, and appendicular. These flaps were compared regarding size, weight, arterial diameter, and lymph node (LN) count after histologic verification. RESULTS: One hundred and sixteen flaps were harvested. The exposed area correlated with the flap weight and volume (r2 = 0.86, r = 0.9). While gastroepiploic LNFs (geLNFs) showed the highest median weight of 99 ml, the jejunal LNFs (jLNFs) had the highest density with 3.8 LNs per 10 ml. The most reliable jLNF was 60 cm from the ligament of Treitz. Three or more LNs were contained in 94% of the jejunal, 88% of the ileal/ileocolic, and 63% of the omental LNs. The ileocolic LNF had the largest arterial diameter of 3 mm, yet the smallest volume. CONCLUSIONS: jLNF and ileal LNF provide a reliable, high LN density for simultaneous, smaller recipient sites. geLNFs are more suitable for larger recipient sites.
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Ganglios Linfáticos/trasplante , Linfedema/cirugía , Colgajos Quirúrgicos , Abdomen/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Ganglios Linfáticos/anatomía & histología , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Recolección de Tejidos y ÓrganosRESUMEN
OBJECTIVE: The purpose of this study was to compare clinical outcomes after vascularized lymph node transfer (VLNT) for the treatment of lymphedema performed on the upper and lower extremities. METHODS: Between April 2015 and January 2020, 71 patients with advanced-stage lymphedema, categorized as International Society of Lymphology late stage 2 or 3, who underwent VLNT in upper and lower extremities were included in this study. Thirty-seven and 34 patients underwent VLNT in upper and lower extremities, respectively. The circumference of the affected and unaffected extremities was measured at baseline, follow-up visits, and at the last visit. The circumference was measured in six places on the extremities, and the circumference and volume percent differences between the affected and unaffected extremities were calculated. First, we compared preoperative and postoperative extremity circumferences in the overall, upper, and lower extremity groups. Second, we compared circumference and volume percent differences between the affected and unaffected extremities calculated at the last visit to identify the degree of improvement by VLNT in the upper and lower extremity groups. RESULTS: The results of the comparative analysis between the preoperative and postoperative extremity circumferences showed that all postoperative extremity circumferences measured at the last visit were decreased compared with the preoperative values in the overall, upper, and lower extremity groups. In the upper extremity group, the circumference percent difference measured at the elbow was 23.1% before surgery and decreased to 13.4% at the last visit (P < .001). In the lower extremity group, the circumference percent difference measured at the knee was 24.4% before surgery and decreased to 17.4% at the last visit (P = .003). In the results of comparative analysis between the upper and lower extremity groups, there was a statistically significant difference in the postoperative circumference percent differences at the elbow/knee calculated at the last visit (P = .048). Similarly, there were statistically significant differences in circumference percent differences in two of six measurement sites at the last visit between the upper and lower extremity groups. However, there was no statistically significant difference in the volume percent difference calculated at the last visit between the upper and lower extremity groups. CONCLUSIONS: These results demonstrate that VLNT may be effective in treating patients with advanced-stage lymphedema. However, patients with upper extremity lymphedema demonstrate superior outcomes compared with those with lower extremity lymphedema.
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Ganglios Linfáticos/irrigación sanguínea , Ganglios Linfáticos/trasplante , Linfedema/cirugía , Anciano , Estudios de Cohortes , Femenino , Humanos , Extremidad Inferior , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Extremidad SuperiorRESUMEN
BACKGROUND: Treatment of secondary lymphedema remains challenging, with suboptimal rates of edema reduction following physiologic procedures (i.e., lymphaticovenous anastomosis and vascularized lymph node transfer). The objective of this study was to investigate the long-term effect of a nanofibrillar collagen scaffold on edema reduction in lymphedema patients treated with lymphaticovenous anastomosis or vascularized lymph node transfer. METHODS: A retrospective cohort study was performed, comparing stage 1 to 3 lymphedema patients who underwent lymphaticovenous anastomosis and/or vascularized lymph node transfer with or without delayed implantation of nanofibrillar collagen scaffold (BioBridge) from 2016 to 2019. The primary endpoint was excess volume reduction. Indocyanine green lymphatic mapping was performed to evaluate superficial lymphatic flow. RESULTS: Edema reduction was significantly greater for the BioBridge cohort (12-month follow-up, n = 18) compared to controls (18.2-month follow-up, n = 11) (111.5 ± 34.5 percent versus 70.0 ± 19.0 percent; p = 0.0004). This held true in lymphaticovenous anastomosis and vascularized lymph node transfer subgroup analysis. The average rate of edema reduction increased by 3.5-fold in lymphaticovenous anastomosis and 7.6-fold in vascularized lymph node transfer following BioBridge placement. Eighty-eight percent of patients with concurrent liposuction and BioBridge implantation maintained normal volumes at 13 months postoperatively. Lymphatic mapping following BioBridge placement showed significantly more new lymphatic collectors and decreased dermal backflow. The majority of patients (77.8 percent) achieved and maintained normal limb volume at an average total follow-up of 29 months. CONCLUSION: Nanofibrillar collagen scaffold implantation enhances overall effectiveness of physiologic procedures, even in the presence of liposuction, and is a promising adjunct therapy for treatment of lymphedema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
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Colágeno/uso terapéutico , Linfedema/terapia , Nanofibras/uso terapéutico , Andamios del Tejido , Adulto , Anciano , Anastomosis Quirúrgica , Estudios de Casos y Controles , Terapia Combinada/métodos , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/irrigación sanguínea , Ganglios Linfáticos/trasplante , Linfangiogénesis , Vasos Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Venas/cirugíaRESUMEN
BACKGROUND: Vascularized lymph node transfer is an efficacious treatment for extremity lymphedema. This study investigated the outcome of retrograde manual lymphatic drainage for vascularized lymph node transfer to distal recipient sites. METHODS: Lymphedema patients who underwent either complete decongestive therapy or vascularized lymph node transfer between 2013 and 2018 were retrospectively included. Retrograde manual lymphatic drainage was started with intermittent manual compression and the assistance of a sphygmomanometer and proximal-to-distal massage of the limb 1 month postoperatively. Outcomes evaluations used the circumferential reduction rate and the Lymphedema-Specific Quality-of-Life Questionnaire. Outcomes of vascularized lymph node transfer to proximal versus distal recipient sites in the literature between 2006 and 2018 were also compared. RESULTS: One hundred thirty-eight unilateral extremity lymphedema patients, including 68 patients in the complete decongestive therapy group and 70 patients in the vascularized lymph node transfer group, were included. The mean circumferential reduction rate of 38.9 ± 2.5 percent in the vascularized lymph node transfer group was statistically greater than the 13.2 ± 10.1 percent rate in the complete decongestive therapy group (p = 0.01). At a mean follow-up of 36 months, the improvement of overall Lymphedema-Specific Quality-of-Life Questionnaire score from 3.8 ± 0.3 to 7.5 ± 1.8 in the vascularized lymph node transfer group was statistically greater than that in the complete decongestive therapy group (from 4.7 ± 0.9 to 5.0 ± 1.9; p < 0.01). In total, 536 lymphedema patients who underwent 548 vascularized lymph node transfers in 23 published articles were reviewed; the distal recipient-site group was found to have more efficacious results than the proximal recipient-site group. CONCLUSION: Vascularized lymph node transfer to a distal recipient site with standard retrograde manual lymphatic drainage significantly improved circumferential reduction rates and Lymphedema-Specific Quality-of-Life Questionnaire scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
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Ganglios Linfáticos/trasplante , Linfedema/terapia , Drenaje Linfático Manual/métodos , Colgajo Perforante/trasplante , Extremidades , Femenino , Humanos , Ganglios Linfáticos/irrigación sanguínea , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Mesenteric lymph nodes (mLNs) are sentinel sites of enteral immunosurveillance and immune homeostasis. Immune cells from the gastrointestinal tract (GIT) are constantly recruited to the mLNs in steady-state and under inflammatory conditions resulting in the induction of tolerance and immune cells activation, respectively. Surgical dissection and transplantation of lymph nodes (LN) is a technique that has supported seminal work to study LN function and is useful to investigate resident stromal and endothelial cell biology and their cellular interactions in experimental disease models. Here, we provide a detailed protocol of syngeneic mLN transplantation and report assays to analyze effective mLN engraftment in congenic recipients. Transplanted mLNs allow to study T cell activation and proliferation in preclinical mouse models. Donor mLNs proved viable and functional after surgical transplantation and regenerated blood and lymphatic vessels. Immune cells from the host completely colonized the transplanted mLNs within 7-8 weeks after the surgical intervention. After allogeneic hematopoietic cell transplantation (allo-HCT), adoptively transferred allogeneic CD4+ T cells from FVB/N (H-2q) mice homed to the transplanted mLNs in C57BL/6 (H-2b) recipients during the initiation phase of acute graft-versus-host disease (aGvHD). These CD4+ T cells retained full proliferative capacity and upregulated effector and gut homing molecules comparable to those in mLNs from unmanipulated wild-type recipients. Wild type mLNs transplanted into MHCII deficient syngeneic hosts sufficed to activate alloreactive T cells upon allogeneic hematopoietic cell transplantation, even in the absence of MHCII+ CD11c+ myeloid cells. These data support that orthotopically transplanted mLNs maintain physiological functions after transplantation. The technique of LN transplantation can be applied to study migratory and resident cell compartment interactions in mLNs as well as immune reactions from and to the gut under inflammatory and non-inflammatory conditions.
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Diferenciación Celular , Proliferación Celular , Enfermedad Injerto contra Huésped/inmunología , Ganglios Linfáticos/trasplante , Activación de Linfocitos , Linfocitos T/trasplante , Enfermedad Aguda , Traslado Adoptivo , Animales , Modelos Animales de Enfermedad , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/metabolismo , Trasplante de Células Madre Hematopoyéticas , Antígenos de Histocompatibilidad Clase II/inmunología , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/metabolismo , Mesenterio , Ratones Endogámicos C57BL , Fenotipo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Tolerancia al Trasplante , Trasplante IsogénicoRESUMEN
BACKGROUND: The lymphatic system plays an active role in modulating inflammation in autoimmune diseases and organ rejection. In this work, we hypothesized that the transfer of donor lymph node (LN) might be used to promote lymphangiogenesis and influence rejection in vascularized composite allotransplantation (VCA). METHODS: Hindlimb transplantations were performed in which (1) recipient rats received VCA containing donor LN (D:LN+), (2) recipient rats received VCA depleted of all donor LN (D:LN-), and (3) D:LN+ transplantations were followed by lymphangiogenesis inhibition using a vascular endothelial growth factor receptor-3 (VEGFR3) blocker. RESULTS: Our data show that graft rejection started significantly later in D:LN+ transplanted rats as compared to the D:LN- group. Moreover, we observed a higher level of VEGF-C and a quicker and more efficient lymphangiogenesis in the D:LN+ group as compared to the D:LN- group. The presence of donor LN within the graft was associated with reduced immunoactivation in the draining LN and increased frequency of circulating and skin-resident donor T regulatory cells. Blocking of the VEGF-C pathway using a VEGFR3 blocker disrupts the lymphangiogenesis process, accelerates rejection onset, and interferes with donor T-cell migration. CONCLUSIONS: This study demonstrates that VCA LNs play a pivotal role in the regulation of graft rejection and underlines the potential of specifically targeting the LN component of a VCA to control graft rejection.
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Rechazo de Injerto/etiología , Ganglios Linfáticos/fisiología , Linfangiogénesis/fisiología , Factor C de Crecimiento Endotelial Vascular/fisiología , Animales , Ganglios Linfáticos/trasplante , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Donantes de Tejidos , Trasplante Homólogo , Factor C de Crecimiento Endotelial Vascular/análisis , Receptor 3 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
INTRODUCTION: Secondary lymphedema is the abnormal collection of lymphatic fluid within subcutaneous structures. Patients with lymphedema suffer a low quality of life. In our study, we aim to provide a systematic review of the current data on patient outcomes regarding breast cancer-related lymphedema (BCRL), and the most prevalent reconstructive techniques. METHODS: A PubMed (MEDLINE) and Scopus literature search was performed in September 2020. Studies were screened based on inclusion/exclusion criteria. The protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO), and it was reported in line with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). RESULTS: The search yielded 254 papers from 2010 to 2020. 67 were included in our study. Lymphaticovenous anastomosis (LVA)-a minimally invasive procedure diverting the lymph into the dermal venous drainage system-combined with postoperative bandaging and compression garments yields superior results with minimal donor site lymphedema morbidity. Vascularized lymph node transfer (VLNT)-another microsurgical technique, often combined with autologous free flap breast reconstruction-improves lymphedema and brachial plexus neuropathies, and reduces the risk of cellulitis. The combination of LVA and VLNT or with other methods maximizes their effectiveness. Vascularized lymph vessel transfer (VLVT) consists of harvesting certain lymph vessels, sparing the donor site's lymph nodes. CONCLUSION: Together with integrated lymphedema therapy, proper staging, and appropriate selection of procedure, safe and efficient surgical techniques can be beneficial to many patients with BCRL.
Asunto(s)
Anastomosis Quirúrgica/métodos , Linfedema del Cáncer de Mama/cirugía , Ganglios Linfáticos/trasplante , Anciano , Linfedema del Cáncer de Mama/clasificación , Linfedema del Cáncer de Mama/etiología , Vendajes de Compresión , Femenino , Humanos , Escisión del Ganglio Linfático/efectos adversos , Microcirugia/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias , Calidad de Vida , Biopsia del Ganglio Linfático Centinela/efectos adversosRESUMEN
BACKGROUND: Lymphoedema after cancer treatment is a chronic and disabling complication that presents a significant health care burden during survivorship with limited treatment options. Vascularised lymph node transfer (VLNT) can reconstruct lymphatic flow to reduce limb volumes, but limited higher-order evidence exists to support its effectiveness. AIM: The aim of the study was to systematically review and meta-analyse the effectiveness of VLNT in reducing upper limb (UL) or lower limb (LL) volume and cellulitis episodes in patients with cancer treatment-related lymphoedema (CTRL). METHODS: PubMed, Medline (Ovid) and Embase databases were searched between January 1974 and December 2019. Full-length articles where VLNT was the sole therapeutic procedure for CTRL, reporting volumetric limb, frequency of infection episodes and/or lymphoedema-specific quality-of-life data, were included in a random-effects meta-analysis of circumferential reduction rate (CRR). Methodological quality was assessed using STROBE/CONSORT, and a novel, lymphoedema-specific scoring tool was used to assess lymphoedema-specific methodological reporting. Sensitivity analyses on the site of VLNT harvest and recipient location were performed. RESULTS: Thirty-one studies (581 patients) were eligible for inclusion. VLNT led to significant limb volume reductions in UL (above elbow pooled CRRs [CRRP] = 42.7% [95% confidence interval (CI): 36.5-48.8]; below elbow CRRP = 34.1% [95% CI: 33.0-35.1]) and LL (above knee CRRP = 46.8% [95% CI: 43.2-50.4]; below knee CRRP = 54.6% [95% CI: 39.0-70.2]) CTRL. VLNT flaps from extra-abdominal donor sites were associated with greater volume reductions (CRRP = 49.5% [95% CI: 46.5-52.5]) than those from intra-abdominal donor sites (CRRP = 39.6% [95% CI: 37.2-42.0]) and synchronous autologous breast reconstruction/VLNT flaps (CRRP = 32.7% [95% CI: 11.1-54.4]) (p < 0.05). VLNT was also found to reduce the mean number of cellulitis episodes by 2.1 episodes per year (95% CI: -2.7- -1.4) and increased lymphoedema-specific quality-of-life scores (mean difference in Lymphoedema-Specific Quality of Life (LYMQOL) "overall domain" = +4.26). CONCLUSIONS: VLNT is effective in reducing excess limb volume and cellulitis episodes in both UL and LL lymphoedema after cancer treatment. However, significant heterogeneity exists in outcome reporting, and standardisation of reporting processes is recommended.
Asunto(s)
Celulitis (Flemón)/cirugía , Aloinjertos Compuestos/irrigación sanguínea , Aloinjertos Compuestos/trasplante , Ganglios Linfáticos/irrigación sanguínea , Ganglios Linfáticos/trasplante , Linfedema/cirugía , Neoplasias/terapia , Alotrasplante Compuesto Vascularizado , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Celulitis (Flemón)/etiología , Celulitis (Flemón)/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Linfedema/etiología , Linfedema/patología , Masculino , Persona de Mediana Edad , Calidad de Vida , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento , Alotrasplante Compuesto Vascularizado/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Changes of the lymph flow from the chest wall after mastectomy and sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (Ax) has yet to be understood. This study aimed to investigate the effect of axillary surgery on lymphatic flow from the chest wall in patients who have undergone mastectomy, including those have undergone breast reconstruction and vascularized lymph node transfer (VLNT). METHODS: Following mastectomy in 100 breasts, the directions of lymph flow from the chest wall was compared between the SLNB omission, SLNB, Ax, and Ax followed by VLNT groups using indocyanine green (ICG) lymphography in cross-sectional study. Lymph flow on the deep epigastric artery perforator (DIEP) flap was also investigated. RESULTS: Lymph flow directing to the ipsilateral axilla was observed more frequently after SLNB than Ax (48% vs. 12.5%; pâ¯=â¯0.005); however, no significant difference was observed in the frequency of contralateral axillary route adoption between them (8% vs. 15%; pâ¯=â¯0.65). In the VLNT group, lymph flow to the ipsilateral axilla was not observed at a significantly higher frequency than in the Ax group (12.5% vs. 12.5%, pâ¯=â¯1.00). On the transferred DIEP flap, the lymph flowed anterograde or retrograde parallel to the anatomic course of the lymphatic vessels. CONCLUSION: To visualize the direction of lymph flow of the chest following mastectomy, ICG lymphography may be useful to discern the direction in which malignant neoplasms, including lymphoma, are transported and to plan for lymph flow restoration.
Asunto(s)
Axila/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Linfografía/métodos , Anciano , Neoplasias de la Mama/patología , Estudios Transversales , Femenino , Humanos , Verde de Indocianina , Escisión del Ganglio Linfático , Ganglios Linfáticos/irrigación sanguínea , Ganglios Linfáticos/trasplante , Metástasis Linfática , Mamoplastia , Mastectomía , Persona de Mediana Edad , Colgajo Perforante/irrigación sanguínea , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND: Lymphatic system is important to maintain homeostasis. Lymph-axiality concept has been reported, which suggests possibility of lymphatic reconstruction using flap transfer without lymph node or supermicrosurgical lymphatic anastomosis. METHODS: Medical charts of 122 free flap reconstruction cases, either with conventional flap transfer (control) or lymph-interpositional-flap transfer (LIFT), for extremity soft tissue defects including lymphatic pathways were reviewed. Lymph vessels' stumps in a flap were placed as close to those in a recipient site as possible under indocyanine green (ICG) lymphography navigation in LIFT group. LIFT group was subdivided into LIFT(+) and LIFT(-) groups; lymph vessels' stumps could be approximated within 2 cm in LIFT(+) group, whereas those could not be in LIFT(-) group. Lymph flow restoration (LFR) and lymphedema development (LED) rates were compared between the groups on postoperative 6 months. RESULTS: No flap included lymph node. LFR was observed in 50 cases and LED in 72 cases. LFR rate in LIFT group (nâ¯=â¯75) was significantly higher than that in control group (nâ¯=â¯47) (57.3% vs. 14.9%; P < 0.001). LED rate in LIFT group was significantly lower than that in control group (20.0% vs. 48.9%; P < 0.001). Sub-group analysis showed significantly higher LFR and lower LED rates in LIFT(+) group (nâ¯=â¯44) than those in LIFT(-) group (nâ¯=â¯31; 88.6% vs. 12.9%; P < 0.001, 4.5% vs. 41.9%; P < 0.001). CONCLUSIONS: LIFT allows simultaneous soft tissue and lymphatic reconstruction without lymph node transfer or lymphatic anastomosis, which prevents development of secondary lymphedema.