Fibro-Lipo-Lymph-Aspiration With a Lymph Vessel Sparing Procedure to Treat Advanced Lymphedema After Multiple Lymphatic-Venous Anastomoses: The Complete Treatment Protocol.

BACKGROUND: In lymphedema, excess adipose tissue occurs with progression of the disease because of chronic lymph stasis, impeding lymphatic flow. Recently, liposuction has been used as a less-invasive procedure to remove this excess tissue. Given the existing poor lymph drainage in patients with lymphatic diseases, extra caution should be taken to avoid damaging lymphatic vessels during liposuction. We developed a new technique (Fibro-Lipo-Lymph-Aspiration with a Lymph Vessel Sparing Procedure [FLLA-LVSP]) to improve chronic swelling in patients with advanced lymphedema. The FLLA-LSVP highlights the superficial lymphatic pathways in the treated limb. This visibility allows surgeons to avoid these pathways, while removing the maximum amount of excess tissue. METHOD: One hundred forty-six patients with primary or secondary lymphedema that had already been treated by lymphatic microsurgery, in Genoa, Italy, were included in this retrospective study. All patients had residual fibrotic/adipose tissue, resistant to conservative treatments. Indocyanine green fluorescent dye and Blue Patent Violet dye were injected laterally/medially to the main superficial veins at the wrist/ankle of the limb to be treated. Using a photodynamic camera, the superficial lymphatic network was made visible and sketched onto the skin in indelible ink. After the microlymphography, the excess adipose tissue was carefully aspirated. Preoperative and postoperative excess limb volume was calculated using circumferential measurements and the formula of a frustum. RESULTS: For the upper limb, 0.80 L, on average, and 2.42 L for the lower limb were removed with the FLLA-LVSP. For the upper limb, there was an average presurgery excess volume of 20.19%, which reduced to 2.68% after the FLLA-LVSP (Z score = -6.90, P < 0.001). Similarly, for the lower limb, there was an average presurgery excess limb volume of 21.24% and a reduction to 2.64% postoperatively (Z score = -3.57, P < 0.01). Immediate postoperative microlymphography and Blue Patent Violet test confirmed no lymphatic complications. No episodes of postoperative infection occurred. CONCLUSIONS: The FLLA-LVSP is efficient. An entire leg can be completed within 90 minutes. Recovery time is short, and cosmetic results are immediate. More importantly, the removal of excess tissue is completed without further damage to lymphatic vessels. When used after microsurgery, FLLA-LVSP offers the possibility of removing almost all obstacles to lymphatic flow.

Mastering Lymphatic Microsurgery: A New Training Model in Living Tissue.

BACKGROUND: Advanced microsurgical techniques have emerged as a promising approach for the treatment of lymphedema, but achieving international standards is limited by a scarcity of adequate training models. The purpose of this report is to describe our in vivo porcine training model for microsurgery. STUDY DESIGN: Five female common-breed pigs (Sus scrofa domesticus) weighing 20 to 28 kg were placed under general anesthesia, and blue patent violet dye was injected to highlight lymphatic structures and prepare the pigs for anatomical exploration and microsurgery. The number and type of patent anastomoses achieved and lymph node flaps created and any anatomical differences between porcine and human vessels were noted, in light of evaluating the use of pigs as a training model for microsurgery in living tissue. RESULTS: Multiple lymphatic-venous anastomoses were created at the site of a single incision made at the subinguinal region, running medial and parallel to the saphenous vessels. Ten multiple lymphatic-venous anastomoses were created in total, and all were demonstrated to be patent. Four lymph node flaps were prepared for lymph node transfer. The superficial lymphatic collector system in the caudal limb of the pig was identified and described with particular reference to the superficial, medial (dominant), and lateral branches along the saphenous vein and its accessory. CONCLUSIONS: The authors present a safe and adaptable in vivo experimental microsurgical porcine model that provides the opportunity to practice several advanced lymphatic microsurgical techniques in the same animal. The ideal lymph node transfer training model can be developed from this anatomical detail, giving the opportunity to use it for artery-to-artery anastomoses, vein-to-vein anastomoses, and lymphatic-to-lymphatic anastomoses.

LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema.

BACKGROUND: Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema. METHODS: Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein. RESULTS: The mean age of patients in the vulvar cancer group was 52 years (range, 48-75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37-56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer. CONCLUSIONS: The LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient's quality of life and decreasing health care costs.

A Single-Site Technique of Multiple Lymphatic-Venous Anastomoses for the Treatment of Peripheral Lymphedema: Long-Term Clinical Outcome.

BACKGROUND: The authors' vast surgical experience in the treatment of primary and secondary peripheral lymphedemas using microsurgical procedures at the Centre of Lymphatic Surgery and Microsurgery of the University of Genoa, Italy, is reported. The objective is to describe the techniques and the long-lasting clinical outcomes based on 40 years' experience and research, with particular reference to advanced derivative and reconstructive lymphatic microsurgery at a single site. METHODS: More than 2,600 patients affected by upper and/or lower limb lymphedema, between 1973 and 2013, underwent lymphatic microsurgery. Derivative multiple lymphatic-venous anastomoses (MLVA) or lymphatic pathway reconstruction using interpositioned vein-grafted shunts multiple lymphatic venous lymphatic anastomoses (MLVLA) were performed at a single site, either the axillary or inguinal-crural region. Patients were followed up for a minimum of 5 years to over 20 years. Clinical outcomes included excess limb volume (ELV), frequency of dermatolymphangioadenitis (DLA) attacks, and use of conservative therapies. RESULTS: Compared with preoperative conditions, patients obtained significant reductions in ELV of over 84%, with an average follow-up of 10 years or more. Over 86% of patients with earlier stages of disease (stage IB or IIA) progressively stopped using conservative therapies and 42% of patients with later stages (stages IIB and III) decreased the frequency of physical therapies. DLA attacks considerably reduced by over 91%. CONCLUSION: MLVA or MLVLA techniques when performed at a single site produce excellent outcomes in the treatment of both primary and secondary lymphedemas, giving the possibility of a complete restoration of lymphatic flow in early stages of disease when tissue changes are minimal.

Microsurgery for groin lymphocele and lymphedema after oncologic surgery.

Groin lymphocele (GL) is a frequent complication of inguinal lymph node dissection, and conservative treatment is not always successful. Different surgical methods have been used to treat lymphoceles arising from lymphatics injured during groin surgery. However, they all involve the closure of lymphatics merging at the lymphocele, increasing the risk of postoperative lower limb lymphedema or of worsening lymphedema if already clinically evident. We assessed the efficacy of a diagnostic and therapeutic protocol to manage inguinal lymphoceles using lymphoscintigraphy (LS) and microsurgical procedures. Sixteen GL [seven associated with leg lymphedema (LL)] were studied by LS preoperatively and treated by complete excision of lymphocele and microsurgical lymphatic-venous anastomoses between afferent lymphatics and a collateral branch of great saphenous vein. Lower limb lymphatics were identified intraoperatively using Patent Blue dye injection. Nine patients without lymphedema had complete healing of lymphocele and no appearance of lower limb postoperative lymphedema. The other seven patients with associated secondary lymphedema had complete disappearance of lymphocele and a remarkable reduction of leg volume. Four of them completely recovered without the need of any compression garment, after the first year postoperative. Inguinal lymphocele nonresponsive to conservative treatment can be advantageously studied by LS and successfully treated by microsurgical reconstructive procedures, above all if associated to LL.

Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: over 4 years follow-up.

Breast cancer-related lymphedema (LE) represents an important morbidity that jeopardizes breast cancer patients' quality of life. Different attempts to prevent LE brought about improvements in the incidence of the pathology but LE still represents a frequent occurrence in breast cancer survivors. Over 4 years ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed and long-term results are reported in this study. From July 2008 to December 2012, 74 patients underwent axillary nodal dissection for breast cancer treatment together with LYMPHA procedure. Volumetry was performed preoperatively in all patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was performed in 45 patients preoperatively and in 30 also postoperatively after at least over 1 year. Seventy one patients had no sign of LE, and volumetry was coincident to preoperative condition. In three patients, LE occurred after 8-12 months postoperatively. Lymphoscintigraphy showed the patency of lymphatic-venous anastomoses at 1-4 years after operation. LYMPHA technique represents a successful surgical procedure for primary prevention of arm LE in breast cancer patients.

Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer.

OBJECTIVE: Lower limb lymphedema (LLL) is the most disabling adverse effect of surgical treatment of vulvar cancer. This study describes the use of microsurgical lymphatic venous anastomosis (LVA) to prevent LLL in patients with vulvar cancer undergoing inguinofemoral lymph node dissection (ILND). METHODS: The study included 8 patients with invasive carcinoma of the vulva who underwent unilateral or bilateral ILND. Before incision of the skin in the inguinal region, blue dye was injected in the thigh muscles to identify the lymphatic vessels draining the leg. Lymphatic venous anastomosis was performed by inserting the blue lymphatics coming from the lower limb into one of the collateral branches of the femoral vein (telescopic end-to-end anastomosis). An historical control group of 7 patients, which underwent ILND without LVA, was used as comparison. After 1 month from the surgery, all patients underwent a lymphoscintigraphy. RESULTS: In the study group, 4 patients underwent bilateral ILND, and 4 patients underwent unilateral ILND. Blue-dyed lymphatics and nodes were identified in all patients. It was possible to perform LVA in all the patients. The mean (SD) time required to perform a monolateral LVA was 23.1 (3.6) minutes (range, 17-32 minutes). The mean (SD) follow-up was 16.7 (6.2) months; there was only 1 case of grade 1 lymphedema of the right leg. Lymphoscintigraphic results showed a total mean transport index were 9.08 and 14.54 in the study and the control groups, respectively (P = 0.092). CONCLUSIONS: This study shows for the first time the feasibility of LVA in patients with vulvar cancer undergoing ILND. Future studies including larger series of patients should clarify whether this microsurgical technique reduces the incidence of LLL after ILND.

Lymphatic microsurgery to treat lymphedema: techniques and indications for better results.

This study aimed to report new clinical approaches to the treatment of lymphatic disorders by microsurgical techniques based on histological and immunohistochemical findings. The authors' wide clinical experience in the treatment of patients with peripheral lymphedema by microsurgical techniques is reported. Microsurgical methods included derivative lymphatic-venous anastomoses and lymphatic reconstruction by interpositioned vein grafted shunts. In all patients, lymphatic and lymph nodal tissues were sent for histological assessment, together with specimen of the interstitial matrix. Diagnostic investigations consisted in venous duplex scan and lymphoscintigraphy. Results were assessed clinically by volumetry performed preoperatively and postoperatively at 3 to 6 months and at 1, 3, and 5 years. The outcome obtained in treating lymphedemas at different stages was analyzed for volume reduction, stability of results with time, reduction of dermatolymphangioadenitis attacks, necessity of wearing elastic supports, and use of conservative measures postoperatively. Microsurgical lymphatic derivative and reconstructive techniques allow bringing about positive results in the treatment of peripheral lymphedema, above all in early stages when tissular changes are slight and allow almost a complete restore of lymphatic drainage.

Surgical prevention of arm lymphedema after breast cancer treatment.

PURPOSE: To prospectively assess the efficacy of the lymphatic microsurgical preventive healing approach (LYMPHA) to prevent lymphedema after axillary dissection (AD) for breast cancer treatment. METHODS: Among 49 consecutive women referred from March 2008 to September 2009 to undergo complete AD, 46 were randomly divided in 2 groups. Twenty-three underwent the LYMPHA technique for the prevention of arm lymphedema. The other 23 patients had no preventive surgical approach (control group). The LYMPHA procedure consisted of performing lymphatic-venous anastomoses (LVA) at the time of AD. All patients underwent preoperative lymphoscintigraphy (LS). Patients were followed up clinically at 1, 3, 6, 12, and 18 months by volumetry. Postoperatively, LS was performed after 18 months in 41 patients (21 treatment group and 20 control group). Arm volume and LS alterations were assessed. RESULTS: Lymphedema appeared in 1 patient in the treatment group 6 months after surgery (4.34%). In the control group, lymphedema occurred in 7 patients (30.43%). No statistically significant differences in the arm volume were observed in the treatment group during follow-up, while the arm volume in the control group showed a significant increase after 1, 3, and 6 months from operation. There was significant difference between the 2 groups in the volume changes with respect to baseline after 1, 3, 6, 12, and 18 months after surgery (every timing P value < 0.01). CONCLUSIONS: LYMPHA represents a valid technique for primary prevention of secondary arm lymphedema with no risk of leaving undetected malignant disease in the axilla.

Lymphangiogenesis and hemangiogenesis: potential targets for therapy.

This review updates historical background from century-old observations on embryonic lymphatic system development through current understanding of the molecular basis of lymphvasculogenesis/lymphangiogenesis ("molecular lymphology"), highlighting similarities and differences with analogous blood vasculature processes. Topics covered include molecular mechanisms in lymphatic development, structural adaptations of the lymphatic vasculature to particulate and cellular transport and trafficking, lymphogenous route of clinical cancer spread, preservation of delineated lymphatic pathways during cancer operations, and anti-lymphangiogenesis in cancer therapy.

Immunohistochemistry in non-immune hydrops fetalis: a single center experience in 79 fetuses.

The objective of our study was to evaluate the usefulness of immunohistochemical (IHC) staining techniques in the etiological diagnosis of non-immune hydrops fetalis (NIHF). The records of all 1,098 autopsies performed between January 1987 and May 2008, by the Division of Fetal Pathology of the University of Genoa, were reviewed and all 79 fetuses diagnosed with NIHF were re-evaluated. Additional IHC staining using antibodies that specifically stain blood and lymph vessels (CD31, CD34, smooth muscle actin antibody, D2-40) were performed. Results were compared to results from the literature. Our results showed that in 67/79 cases, evaluation by standard autopsy protocol led to an etiologic diagnosis. Furthermore, we were able to identify the pathogenetic mechanisms that eventually caused NIHF in 42/79 cases. Adding IHC staining to all evaluations identified the pathogenetic mechanism in a further 17 cases (total 59/79 cases). Lymphatic dysplasia was diagnosed by standard autopsy protocol in 1/79 (1.3%), while adding IHC staining resulted in 18/79 (22.8%) cases being diagnosed (P = 0.0001). The present rate of 22.8% of lymphatic dysplasia in non-immune hydrops fetalis is significantly higher than reported in the literature (36/818 or 4.4%; P = 0.01). In conclusion, specific IHC staining techniques aimed at detecting lymphatic dysplasia are needed and should be mandatory in autopsies of fetuses with non-immune hydrops fetalis.

Microsurgery for lymphedema: clinical research and long-term results.

OBJECTIVES: To report the wide clinical experience and the research studies in the microsurgical treatment of peripheral lymphedema. METHODS: More than 1800 patients with peripheral lymphedema have been treated with microsurgical techniques. Derivative lymphatic microvascular procedures recognize today its most exemplary application in multiple lymphatic-venous anastomoses (LVA). In case of associated venous disease reconstructive lymphatic microsurgery techniques have been developed. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. RESULTS: Subjective improvement was noted in 87% of patients. Objectively, volume changes showed a significant improvement in 83%, with an average reduction of 67% of the excess volume. Of those patients followed-up, 85% have been able to discontinue the use of conservative measures, with an average follow-up of more than 10 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. CONCLUSIONS: Microsurgical LVA have a place in the treatment of peripheral lymphedema, and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment.

Diagnostic assessment and therapeutic approach for immunodeficiency due to chylous dysplasia: A case report.

Among possible causes of a condition of immunodeficiency, we have to consider the presence of a serious chylous dysplasia, due to the great loss of proteins through the intestinal lumen. A 20-year-old male, suffered from diarrhoea (2-4 times a day), weight loss (8 kilos in 5 years), and malnutrition (hypogammaglobulinemia, hypoalbuminemia, leukocytopenia with lymphocytopenia). Accurate diagnostic assessment allowed to diagnose a protein-losing enteropathy. Conventional oil contrast lymphangiography allowed to accurately assess the case and to establish a proper therapeutic approach. The operation consisted in multiple antigravitational ligatures of dilated and incompetent chylous vessels and chylous vessel-mesenteric vein microanastomoses. Parameters concerning albumin and leukocytes normalized in 1 week after operation and remained stable with time; there were no more episodes of diarrhoea and the patient recovered weight. An accurate diagnostic assessment and above all lymphangiography allow to diagnose properly difficult cases of immunodeficiency due to intestinal protido-dispersion and to plan a correct therapeutic functional approach.

Lymphedema microsurgical preventive healing approach: a new technique for primary prevention of arm lymphedema after mastectomy.

BACKGROUND: The purpose of this manuscript is to assess the efficacy of direct lymphatic venous microsurgery in the prevention of lymphedema following axillary dissection for breast cancer. METHODS: Nineteen patients with operable breast cancer requiring an axillary dissection underwent surgery, carrying out LVA between the blue lymphatics and an axillary vein branch simultaneously. The follow-up after 6 and 12 months from the operation included circumferential measurements in all cases and lymphangioscintigraphy only in 18 patients out of 19 cases. RESULTS: Blue nodes in relation to lymphatic arm drainage were identified in 18/19 patients. All blue nodes were resected and 2-4 main afferent lymphatics from the arm could be prepared and used for anastomoses. Lymphatic-venous anastomoses allowed to prevent lymphedema in all cases. Lymphangioscintigraphy demonstrated the patency of microvascular anastomoses. CONCLUSIONS: Disruption of the blue nodes and closure of arm lymphatics can explain the significantly high risk of lymphedema after axillary dissection. LVA proved to be a safe procedure for patients in order to prevent arm lymphedema.

Nuchal translucency and lymphatic system maldevelopment.

We describe the histological examination of 18 aborted fetuses that had increased nuchal translucency (NT) between 11(+0) and 13(+6) weeks' gestation. The aim of this study was to assess the corresponding NT anatomic features by immunohistochemical (IHC) investigation. A morphological study was performed using lymphatic and blood endothelial specific markers, as well as smooth muscle actin (SMA). We found that all 18 cases were D2-40 positive, CD31 positive, and CD34 negative, suggesting the presence of nuchal lymph vessel ectasia. We found that 12/18 cases were SMA staining positive and 6/18 cases were SMA negative, suggesting that 6/18 cases had nuchal cystic lymphangiectasia, whereas 12/18 had cystic hygromas. The present data seem to confirm the reasonable hypothesis that lymphangiogenesis plays a relevant role in nuchal edema, increased NT, and that increased NT is the result of a lymphatic malformation or a delayed development of the lymphatic system.

Rationale for Study of the Deep Subfascial Lymphatic Vessels During Lymphoscintigraphy for the Diagnosis of Peripheral Lymphedema.

PURPOSE: The current study aimed to determine the utility of including the study of deep subfascial lymphatic vessels in a 2-compartment lymphoscintigraphy for the diagnosis of lymphedema in patients with limb swelling. Lymphoscintigraphy is a valuable imaging tool for the timely diagnosis of peripheral lymphedema. However, there is a lack of standardization in its application, especially regarding which type of lymphatic vessels to examine (superficial, deep, or both). METHODS: Two hundred fifty-eight patients with lymphedema underwent segmental lymphoscintigraphy. The transport index (TI) was calculated to categorize the flow of the superficial and deep vessels as normal (<10) or pathological (≥10). The scores from 248 patients (48 unilateral arm, 86 unilateral leg, 114 bilateral leg) were tested with a 3-way analysis of variance to examine the relationship between affected limb, deep or superficial pathways, and primary or secondary lymphedema. The relationship between clinical presentation and TI was also investigated. RESULTS: In general, primary and secondary lymphedema patients had similar patterns of lymphoscintigraphic lymphatic abnormalities. Patients with unilateral clinical presentation can have bilateral TI abnormalities. The vast majority of patients (88%-98%) had either the deep subfascial vessels alone, or both the superficial and deep vessels, with a pathological TI. CONCLUSIONS: A 2-compartment lymphoscintigraphy is able to accurately detect lymphatic flow abnormalities in patients with limb swelling. Given that the vast majority of patients had deep lymphatic vessels abnormalities, inclusion of these vessels in the lymphoscintigraphic diagnostic protocol is recommended.

Lymphatic dysplasias in newborns and children: the role of lymphoscintigraphy.

We performed lymphoscintigraphy in 15 patients (newborns and children) affected by congenital lymphatic dysplasia. We suggest that lymphoscintigraphy is mandatory in all patients with signs of lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, to obtain very early diagnosis and begin treatment.