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The Campisi Approach for Lymphatic Surgery

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Abstract

“Single-site” microsurgical derivative and reconstructive lymphatic-venous anastomoses (multiple lymphatic-venous anastomoses [MLVA] and multiple lymphatic-venous-lymphatic anastomoses) can result in effective functional repair of the lymphatic pathways by diverting the lymph into adjacent veins proximal to the source of lymphatic obstruction. The single-site MLVA approach developed by Campisi et al. is particularly appropriate for most patients with lymphedema, as it uses both superficial and deep lymphatic vessels. Recent research has indicated that the majority of patients with lymphedema have pathological drainage affecting the deep lymphatic vessels. MLVA lymphatic microsurgery is most effective when applied early in the disease course and when performed in conjunction with a combined treatment protocol like complete lymphedema functional treatment.

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Secondary lymphedema of the upper and lower extremities related to prior oncologic therapies, including cancer surgeries, radiation therapy, and chemotherapy, is a major cause of long-term morbidity in cancer patients. For the upper extremities, it is most commonly associated with prior oncologic therapies for breast cancer, while for the lower extremities, it is most commonly associated with oncologic therapies for gynecologic cancers, urologic cancers, melanoma, and lymphoma. Both non-surgical and surgical management strategies have been developed and utilized, with the primary goal of all management strategies being volume reduction of the affected extremity, improvement in patient symptomology, and the reduction/elimination of resultant extremity-related morbidities, including recurrent infections. Surgical management strategies include: (i) ablative surgical methods (i.e., Charles procedure, suction-assisted lipectomy/liposuction) and (ii) physiologic surgical methods (i.e., lymphaticolymphatic bypass, lymphaticovenular anastomosis, vascularized lymph node transfer, vascularized omental flap transfer). While these surgical management strategies can result in dramatic improvement in extremity-related symptomology and improve quality of life for these cancer patients, many formidable challenges remain for successful management of secondary lymphedema. It is hopeful that ongoing clinical research efforts will ultimately lead to more complete and sustainable treatment strategies and perhaps a cure for secondary lymphedema and its devastating resultant morbidities.
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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.
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Recent advances in surgical management of lymphedema have provided options for patients who have failed conservative management with manual lymphatic massage and/or compression garments. The purpose of this review is to provide a historical background to the surgical treatment of lymphedema and how these options have evolved over time. In addition, we aim to delineate the various types of surgical approaches available, indications for surgery, and reported outcomes. Our goal is to increase awareness of these options and foster research to improve their outcomes.
Article
Introduction Lymphoscintigraphy is the gold standard for imaging in the diagnosis of peripheral lymphedema. However, there are no clear guidelines to standardize usage across centers, and as such, large variability exists. The aim of this perspectives paper is to draw upon the knowledge and extensive experience of lymphoscintigraphy here in Genoa, Italy, from our center of excellence in the assessment and treatment of lymphatic disorders for over 30 years to provide general guidelines for nuclear medicine specialists. Method The authors describe the technical characteristics of lymphoscintigraphy in patients with limb swelling. Radioactive tracers, dosage, administration sites, and the rationale for a two-compartment protocol with the inclusion of subfascial lymphatic vessels are all given in detail. Results Examples of lymphoscintigraphic investigations with various subgroups of patients are discussed. The concept of a transport index (TI) for semi-quantitative analysis of normal/pathological lymphatic flow is introduced. Different concepts of injection techniques are outlined. Discussion It is past time that lymphoscintigraphy in the diagnosis of lymphatic disorders becomes standardized. This represents our first attempt to outline a clear protocol and delineate the relevant points for lymphoscintigraphy in this patient population.
Article
Background End‐stage lower extremity lymphedema (LEL) poses a particularly formidable challenge to surgeons as multiple pathological processes are at work. Because single modality treatment is often unsuccessful, we devised a comprehensive multimodal surgical treatment. The aim of this study is to share the technical considerations and examine the clinical outcomes of this combined approach. Methods Between 2013 and 2017, patients with International Society of Lymphology stage III, who underwent the combination treatment of Charles,’ Homan’s procedure with toe management and vascularized lymph node transfer (CHAHOVA), were included in this retrospective study. Outcomes evaluated were limb size, number of infectious episodes, compression garment usage, and rate of complications. Results A total of 68 patients were included. With a mean follow‐up of 29 months, the overall circumference reduction rate for the upper thigh and the rest of the extremity was 67.4% (48.2‐88.2%) and 98.1% (88‐100%), respectively. During the follow‐ups, 2 (2.9%) patients experienced episodes of cellulitis and the average number of yearly infections decreased from 4.2 to 1.2 episodes per person. All patients were able to discontinue compression therapy without recurrence of lymphedema. Nine (13.2%) patients reported minor complications. Conclusion The combine CHAHOVA in a single‐stage procedure is an effective and safe approach in the end‐stage LEL.
Article
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.
Article
Background Although conservative management of lymphedema remains the first-line approach, surgery is effective in select patients. The purpose of this study was to review the literature and develop a treatment algorithm based on the highest quality lymphedema research. Methods A systematic literature review was performed to examine the surgical treatments for lymphedema. Studies were categorized into five groups describing excision, liposuction, lymphovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and combined/multiple approaches. Studies were scored for methodological quality using the methodological index for nonrandomized studies (MINORS) scoring system. Results A total of 69 articles met inclusion criteria and were assigned MINORS scores with a maximum score of 16 or 24 for noncomparative or comparative studies, respectively. The average MINORS scores using noncomparative criteria were 12.1 for excision, 13.2 for liposuction, 12.6 for LVA, 13.1 for VLNT, and 13.5 for combined/multiple approaches. Loss to follow-up was the most common cause of low scores. Thirty-nine studies scoring > 12/16 or > 19/24 were considered high quality. In studies measuring excess volume reduction, the mean reduction was 96.6% (95% confidence interval [CI]: 86.2–107%) for liposuction, 33.1% (95% CI: 14.4–51.9%) for LVA, and 26.4% (95% CI: − 7.98 to 60.8%) for VLNT. Included excision articles did not report excess volume reduction. Conclusion Although the overall quality of lymphedema literature is fair, the MINORS scoring system is an effective method to isolate high-quality studies. These studies were used to develop an evidence-based algorithm to guide clinical practice. Further studies with a particular focus on patient follow-up will improve the validity of lymphedema surgery research.
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Objective Currently, lymphedema (LED) is typically diagnosed clinically on the basis of a patient's history and characteristic physical findings. Whereas the diagnosis of LED is sometimes confirmed by lymphoscintigraphy (LSG), the technique is limited in both its ability to identify disease and to guide therapy. Recent advancements provide opportunities for new imaging techniques not only to assist in the diagnosis of LED, based on anatomic changes, but also to assess contractile function and to guide therapeutic intervention. The purpose of this contribution was to review these imaging techniques. Methods Literature for each technique is reviewed and discussed, and the evidence for each of these new diagnostic techniques was assessed on several criteria to determine if each could (1) establish whether disease is present, (2) determine the severity of the disease process, (3) define the pathophysiologic mechanism of the disease process, (4) demonstrate whether intervention is possible as well as what type, and (5) objectively grade the response to therapy. Results LSG is currently the standard test to confirm LED. Duplex ultrasound (DUS) is a simple, readily available noninvasive test that can identify LED by specific tissue characteristics as well as the response to therapy. Magnetic resonance imaging and computed tomography scans similarly demonstrate the alterations in epidermal and subcutaneous tissue, but the latter can also detect obstructing neoplasms as a cause of secondary LED. Moreover, magnetic resonance lymphangiography details lymphatic vessels and nodes and their function. Newer fluorescence imaging techniques provide opportunities to image lymphatic anatomy and function. Visible microlymphangiography by fluorescein sodium is limited by tissue light absorption to imaging depths of 200 μm. Near-infrared fluorescence lymphatic imaging, a newer test using intradermal injection of indocyanine green, can penetrate several centimeters of tissue and can visualize the initial and conducting lymphatics, the lymph node basins, and the active function of lymphangions (the key module) in exquisite detail. Conclusions The availability and the noninvasive nature of DUS should make this modality the first choice for establishing the diagnosis of LED based on tissue changes. Further studies comparing DUS with LSG, however, are needed. The costs of magnetic resonance imaging and computed tomography limit their adoption as a means to regularly assess the lymphatics. Whereas lymphatic truncal anatomy and transit times can be delineated by the older technique of LSG, near-infrared fluorescence lymphatic imaging is rapid, highly sensitive, and repeatable and provides exquisite detail for lymphatic vessel anatomy and function of the lymphangions as well as the response to therapy.
Article
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.
Article
Intermittent negative pressure devices were initially developed by NASA to enhance blood perfusion and combat a reduction in orthostatic tolerance. Investigational studies have demonstrated that the pressure differential produces changes in the blood and cardiac systems and also documented changes in weight and cellulite in obese patients. Although the mechanisms are not known, previous investigation has also reported changes in lymphedematous limbs. These initial results suggested to us that the inclusion of intermittent negative pressure into a lymphedema treatment protocol would be beneficial. We subsequently undertook a study of 50 patients with lymphedema adding intermittent negative pressure to our CLyFT protocol and compared them to the CLyFT protocol without intermittent negative pressure. We found a significant difference between the groups with an additional 7% reduction in lymphedema volume (p=0.008). Our study results indicate that the inclusion of intermittent negative pressure therapy into the CLyFT protocol was beneficial and further incorporation into other protocols should be investigated. © 2015, International Society of Lymphology. All rights reserved.
Article
Background: Free vascularized lymph node transfer (VLNT) is a relatively novel technique for treatment of lymphedema. The purpose of this systematic review was to evaluate the current evidence on VLNT and to determine if there is objective data concerning improved outcomes. Methods: A literature search of PubMed, EMBASE and CENTRAL electronic databases was conducted to identify articles written in the English language on VLNT for treatment of lymphedema. Publications were selected according to inclusion criteria. Papers reporting adjunct techniques and those that did not describe outcomes were excluded. Data including patient demographics, surgical technique, complications and outcomes were extracted. A quality score was calculated for each article. Results: Eighteen studies were included with an overall study population of 305 patients. Mean quality score of articles was 5.3 with levels of evidence range from II to IV. Among 182 patients who underwent limb circumference assessment, 165 (91%) showed postoperative improvement. Reduction of limb volume was noted in 98 of 114 (86%) patients. Ninety two patients underwent lymphoscintigraphy/lymphangiography and 55 (60%) demonstrated moderate or significant improvement of flow. Patient satisfaction was questioned in 105 patients and with exception of 7 patients, all reported a high satisfaction level with significant relief in symptoms and improved quality of life. Publications also reported a reduction in infectious episodes. Conclusion: VLNT appears to provide improvement in lymphedema. More studies with standardized methods for reporting outcomes and uniform patient selection are needed to evaluate this technique thoroughly.
Article
Treatment of primary lower extremity lymphedema (LEL) is challenging, and lymph node transfer (LNT) can be a choice of treatment for progressive LEL. However, LNT has a risk of donor site lymphedema and possible lymph node (LN) sclerosis due to efferent lymphatic vessel (ELV) obstruction. We report the first case of complete lymph flow reconstruction with true perforator LNT with efferent lymphaticolymphatic anastomosis (ELLA) for a primary LEL case with severe lymphosclerosis. A 49-year-old female suffered from primary progressive unilateral left LEL refractory to conservative treatments with frequent episodes of cellulitis. A true perforator LN flap was selectively harvested from the left lateral thoracic region under indocyanine green (ICG) lymphography navigation, and transferred to the left groin with perforator-to-perforator anastomosis. The ELV of the transplanted LN was supermicrosurgically anastomosed to the contralateral iliac lymphatic vessel which was subcutaneously transferred to the left groin. Postoperatively, the patient experienced no episode of cellulitis with reduced degree of compression treatment, and lymphedematous volume decreased from 306 to 264 in LEL index. Postoperative ICG lymphography showed evidence of reconstructed lymph flow from the left foot to the left groin, and to the right inguinal LN through the transplanted LN flap and the ELLA. There were no subjective or objective findings of donor site lymphedema of the left arm or the right back and lower extremity. True perforator LN flap with ELLA is a safe and effective treatment, and has a potential to be a useful therapeutic option for primary unilateral LEL.
Article
Introduction: Lymphedema remains a challenging clinical problem. A new field of lymphatic surgery using micro and super microsurgery techniques is a rapidly advancing field aimed to treat recalcitrant cases. The objective of this study was to evaluate outcomes and complications of vascularized lymph node transfer (VLNT). Several early preliminary studies have reported promising outcomes, but they are limited by small numbers, short follow-up, and are inconsistent in addressing the origin and recipient site of the transferred lymph nodes as well as the donor site morbidity. Methods: A review of literature was conducted using PubMed-MEDLINE, EMBASE for key words vascularized lymph node transfer (also autologous, lymph node transplant). Only human studies were included. Results: A total 24 studies encompassing 271 vascularized lymph node transfers were included. The inguinal nodes were the most commonly used donor site followed by the lateral thoracic lymph nodes. The lateral thoracic lymph nodes were the least effective and had the highest complication rates (27.5%) compared to other lymph node donor sites (inguinal: 10.3% and supraclavicular: 5.6%). Upper extremity lymphedema responded better compared to lower extremity (74.2 vs. 53.2%), but there was no difference in placing the lymph nodes more proximally versus distally on the extremity (proximal: 76.9% vs. distal: 80.4%). Conclusion: Vascularized lymph node transfer for lymphedema treatment is a promising operative technique showing beneficial results in early but also in advanced stage lymphedema. This physiologic surgical procedure should be included in a modern reconstructive concept for lymphedema treatment. © 2016 Wiley Periodicals, Inc. Microsurgery, 2016.
Article
The B.A.S. (Big Angiodysplastic Syndromes) are analysed with 1° or 2° Lymphedema or both, the meaning of the angiodysplasia in the function of the Lymphatic sistem. Seven points are remarket, on wich task forces have to plan action with priority, the study of angiotumorogenesis and inhibitor factors, the treatment of the vascular or tissue hypertension, their risks, technical (7) strategic alternatives and protocols in 1° and 2° coagulopathies.
Article
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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article
Aim: The aims of this prospective study were (a) to examine the relationship between pre-operative muscle lymph flow and the predisposition to BCRL in women treated by axillary nodal surgery for breast cancer; and (b) to test the 'stopcock' hypothesis that axillary lymph node surgery impairs forearm lymph flow in the short term. Methods: (99m)Tc-nanocoll was injected intramuscularly into both forearms of women undergoing surgery for breast cancer. Lymphatic clearance rate constant, k, representing lymph flow per unit interstitial fluid volume, was measured as the fractional disappearance rate of radioactivity from the depot site by gamma camera imaging. Axillary lymph node activity was calculated as percentage injected activity. BCRL was assessed by clinical examination and upper limb perometry. Results: Of 38 pre-operative women, 33 attended at 8 ± 6 weeks post-operatively and 31 at 58 ± 9 weeks post-operatively. Seven patients (18%) developed BCRL. Prior to surgery the BCRL-destined patients had a higher mean k (0.0962 ± 0.034%/min) than non-BCRL patients (0.0830 ± 0.019%/min) (p = 0.10, unpaired t test). Post-operative k values were not significantly different from pre-operative, in either the ipsilateral (operated) or contralateral limb. Also, post-operative k values did not differ significantly between both upper limbs. Furthermore, there was no significant difference between pre- and post-operative axillary activity. Conclusion: Patients who develop BCRL have high lymph flow pre-surgery, which may predispose them to lymphatic overload and failure. Axillary lymph node surgery has no early, measurable effect on forearm muscle lymph flow despite surgical disruption of routes of lymph drainage.
Article
Microvascular lymph node transfer has been used to improve lymphatic function in patients with lymphoedema. We previously reported changes in the lymphatic function of the donor limb after lymph node transfer. For this reason, we modified our surgical method to be more conservative. Microvascular lymph node transfer was performed in 13 patients using the previously reported original method. Sixteen patients were operated upon using the more conservative modified method. Lymphatic function in the donor limb was evaluated using volumetry, lymphoscintigraphy and tissue water percentage. In the original method group, the donor-limb volume was on average greater (199 ± 540 ml) than in the non-operated control limb. The volume difference between the limbs was smaller (151 ± 463 ml) in the modified method group. Two patients in the original method group had abnormal transport index (Ti) values in lymphoscintigraphy indicating decreased lymphatic function of the donor limb. In the modified method group, the Ti-values remained normal. The tissue water percentage of the donor limb was on average 40% ± 4% in the original method group and 40% ± 3% in the modified method group. Importantly, none of the patients in either group developed clinical lymphoedema in the donor limb during the 11-84-month follow-up. Even with the more conservative lymph node transfer method, we can observe slight, subclinical signs of lymphatic dysfunction in the donor limb. These results highlight the importance of minimizing the surgical exploration in the inguinal area and avoiding damage to the lymphatic vessels or sentinel nodes draining the lower limb. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Article
Objective: A comprehensive literature review of VLNT with updates and comparisons on current application, techniques, results, studies and possible future implications. Background: Lymphedema is a debilitating condition that often results secondary to treatment of cancer. Unfortunately there is no cure. However, microsurgical procedures such as VLNT has gained popularity as there have been increasing reports that VLNT may help alleviate the severity of lymphedema. Methods: A review of literature was conducted over major medical indices (PubMed-MEDLINE, Factiva, Scopus, Sciencedirect, EMBASE). Search terms were focused on vascularized, lymph node transfer (also autologous, lymph node transplant) to cover both human and animal studies. Each study was verified for the nature of the procedure; a free microsurgical flap containing lymph nodes for the purpose of relieving lymphedema. Results: There are human and animal studies that individually report clear benefits, but because of methodological shortcomings comparative studies with uniform patient selection and monitoring are lacking. Conclusions: Although the results with the use of VLNT for treatment of lymphedema have been largely positive, further exploration into standardized protocols for diagnosis, treatment optimization, and patient outcomes assessment is needed.
Article
Lymphedema is the chronic, progressive enlargement of tissue due to inadequate lymphatic function. Although lymphedema is a specific condition, patients with a large extremity are often labeled as having "lymphedema," regardless of the underlying cause. The purpose of this study was to characterize referrals to a center to determine if lymphedema should be managed by specialists. Patients treated in our Lymphedema Program between 2009 and 2013 were reviewed. Diagnosis was determined based on history, physical examination, photographs, and imaging studies. Lymphedema type (primary or secondary), location of swelling, patient age, sex, and previous management were documented. The accuracy of referral diagnosis and the geographic origin of the patients also were analyzed. Two hundred twenty-five patients were referred with a diagnosis of "lymphedema"; 71% were women and 29% were children. Lymphedema was confirmed in 75% of the cohort: primary (49%) and secondary (51%). Twenty-five percent of patients labeled with "lymphedema" had another condition. Before referral 34% of patients with lymphedema received tests that are nondiagnostic for the disease, and 8% were given a diuretic which does not improve the condition. One third of patients resided outside our local referral area. The average time between onset of lymphedema and referral to our Lymphedema Program was 7.7 years (range, 1-59 years). Patients presenting to a center with "lymphedema" often have another condition, and may be suboptimally managed before their referral. Patients with suspected lymphedema should be referred to specialists focused on this disease.
Article
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. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014.
Article
Vascularized lymph node flap transfer for the treatment of upper and lower limb lymphedema has had promising results. This study was performed to investigate the mechanism of lymph drainage of a vascularized lymph node flap both experimentally and clinically. In the experimental study, 18 Sprague-Dawley rats were used to create 36 flaps, either a groin lymph node flap or an abdominal cutaneous flap that did not contain lymph nodes. Indocyanine green dye was injected into the edge of 12 lymph node flaps, directly into a lymph node of 12 lymph node flaps, and into the edge of 12 cutaneous flaps. In the clinical study, an identical study design was used, with 24 vascularized lymph node flaps and 12 cutaneous flaps not containing lymph nodes. Experimentally, fluorescence was detected in the pedicle vein after a mean latency period of 153 ± 129 seconds when the edge of the lymph node flap was injected and 12.8 ± 8.1 seconds when the lymph node was directly injected. Fluorescence was not detected in the pedicle vein of the cutaneous flaps (p < 0.01). Clinically, fluorescence was detected in the pedicle vein after a mean latency period of 346 ± 249 seconds when the edge of the lymph node flap was injected and 23.5 ± 27.1 seconds when the lymph node was directly injected. Fluorescence was not detected in the pedicle vein of the cutaneous flaps (p < 0.01). The vascularized lymph node flap drains lymph into the pedicle vein, both experimentally and clinically. Therapeutic, V.
Article
Despite the development of minimal access dissection techniques, use of superficial groin dissection alone, and other recommendations to reduce morbidity in melanoma treatment, the incidence of lymphedema is still significant. The purpose of the current study was to assess the efficacy of microsurgical methods to limit the morbidity of inguinal lymphadenectomy. We conducted a retrospective review of patients who underwent groin dissection for melanoma treatment from February 2006 to April 2009. A total of 59 melanoma patients with positive groin lymph nodes comprised 18 patients (T-group) with melanoma in the trunk and 41 patients (E-group) who had melanoma in an extremity and currently have lymphedema. The T-group patients underwent primary prevention of lymphedema with microsurgical lymphatic-venous anastomoses (LVA) performed simultaneously with groin dissection. The E-group patients underwent LVA to treat the secondary lymphedema after an accurate oncological and lymphological assessment. Limb volume measurements and lymphoscintigraphy were performed pre- and postoperatively to assess short and long term outcome. No lymphedema occurred after microsurgical primary preventive approach in the T- group. Significant (average 80% reduction of pre-op excess volume) reduction of lymphedema resulted after microsurgical treatment for secondary leg lymphedema. Post-operative lymphoscintigraphy in 35 patients demonstrated patency of microsurgical anastomoses in all cases with an average follow-up of 42 months. Study results demonstrate that microsurgical LVA primary prevention prevented lymphedema after inguinal lymphadenectomy in the T-group patients. In addition, lymphatic-venous multiple anastomoses proved to be a successful treatment for clinical lymphedema with particular success if treated at the early stages.
Article
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. © 2013 Wiley Periodicals, Inc. Microsurgery, 2013.
Article
OBJECTIVE: This study aims to assess potential complications of autologous lymph-node transplantation (ALNT) to treat limb lymphoedema. DESIGN: Prospective, observational study. METHOD: All limb-lymphoedema patients, followed up in a single lymphology department, who decided to undergo ALNT (January 2004-June 2012) independently of our medical team, were included. RESULTS: Among the 26 patients (22 females, four males) included, 14 had secondary upper-limb lymphoedema after breast-cancer treatment and seven had secondary and five primary lower-limb lymphoedema. Median (interquartile range, IQR) ages at primary lower-limb lymphoedema and secondary lymphoedema onset were 18.5 (13-30) and 47.4 (35-58) years, respectively. Median body mass index (BMI) was 25.9 (22.9-29.3) kg m(-2). For all patients, median pre-surgery lymphoedema duration was 37 (24-90) months. Thirty-four ALNs were transplanted into the 26 patients, combined with liposuction in four lower-limb-lymphoedema patients. Ten (38%) patients developed 15 complications: six, chronic lymphoedema (four upper limb, two lower limb), defined as ≥2-cm difference versus the contralateral side, in the limb on the donor lymph-node-site territory, persisting for a median of 40 months post-ALNT; four, post-surgical lymphocoeles; one testicular hydrocoele requiring surgery; and four with persistent donor-site pain. Median (IQR) pre- and post-surgical lymphoedema volumes, calculated using the formula for a truncated cone, were, respectively, 1023 (633-1375) ml (median: 3 (1-6) months) and 1058 (666-1506) ml (median: 40 (14-72) months; P = 0.73). CONCLUSION: ALNT may engender severe, chronic complications, particularly persistent iatrogenic lymphoedema. Further investigations are required to evaluate and clearly determine its indications.
Article
Background: Upper limb lymphedema is one of the most underestimated and debilitating complications of breast cancer treatment. The aim of this review is to summarize the recent literature for evidence of the effectiveness of lymphatic microsurgery for the treatment of breast cancer-related lymphedema (BCRL). Methods: A search was conducted for articles published from January 2000 until January 2012. Only studies on secondary lymphedema after breast cancer treatment and those examining the effectiveness of microsurgery were included. Results: No randomized clinical trials or comparative studies were available. Ten case-series met inclusion criteria: (composite) tissue transfer (n = 4), lymphatic vessel transfer (n = 2), and derivative microlymphatic surgery (n = 4). Limb volume/circumference reduction varied from 2 to 50% over a follow-up time ranging from 1 to 132 months. Postoperative discontinuation rates of conservative therapy were only reported after composite tissue transfer, ranging from 33 to 100% after 3 to 24 months. Clear selection criteria for lymphatic surgery and lymphatic flow assessment were absent in most studies. Conclusion: We identified important methodological shortcomings of the available literature. Evidence acquired through comparative studies with uniform patient selection is lacking. Consistent positive findings with regards to limb volume reduction and limited complications are reasons to further explore these techniques in methodologically superior studies.
Article
The problem of prevention of lymphatic complications in surgery is extremely important if we think about the frequency of both early complications such as lymphorrhea, lymphocele, wound dehiscence and infections and late complications such as lymphangitis and lymphedema. Nowadays, it is possible to identify risk patients and prevent these lesions or treat them at an early stage. This report helps to demonstrate how it is important to integrate diagnostic and clinical findings to better understand how to properly identify risk patients for lymphatic injuries and, therefore, when it is useful and proper to do prevention. Authors report their experiences in the prevention and treatment of lymphatic injuries after surgical operations and trauma. After an accurate diagnostic approach, prevention is based on different technical procedures among which microsurgical procedures. It is very important to follow-up the patient not only clinically but also by lymphoscintigraphy. A protocol of prevention of secondary limb lymphedema was proposed and it includes, from the diagnostic point of view, lymphoscintigraphy and, as concerns therapy, it recognizes also a role to early microsurgery. It is necessary to accurately follow-up the patient who has undergone an operation at risk for the appearance of lymphatic complications and, even better, to assess clinically and by lymphoscintigraphy the patient before surgical operation.
Article
Background: Chronic lymphoedematous limbs have an increased propensity for infections and primary or secondary malignant tumours. It has been attributed to suppressed delayed-type hypersensitivity measured in lymphoedemas related to Stewart-Treves syndrome, Kaposi's sarcoma or breast cancer treatment. Cell-mediated immunity is an effective defence mechanism against bacteria, fungi, viruses and tumour cells. Objective: We aimed to examine whether decongestive lymphoedema therapy could improve cell-mediated immunity in breast cancer treatment-related lymphoedema (BCRL). Methods: Eight women with unilateral BCRL were included in this study. At baseline, tuberculin skin test (TST) was performed on the volar surfaces of the forearms of the affected and non-affected sides using 0.5, 1 and 5 tuberculin units in the form of three consecutive injections with 3-cm spaces in-between, and arm volumes were measured using the Kuhnke's disc model. Decongestive lymphatic therapy was given to swollen arms in 10 consecutive working days. At the end of intensive decongestion, TST on affected side and bilateral volumetry were repeated. Results: Baseline test using undiluted (5 units) and fivefold diluted (1 unit) tuberculin solutions has shown significant differences (P < 0.05) between the mean sizes (11.81 ± 2.32 and 7.75 ± 1.92; 7.12 ± 1.12 and 5.12 ± 0.91 respectively) in favour to healthy arms. Post therapeutically, the mean sizes were significantly increased (P < 0.05) in the dilutions of 1 : 1 and 1 : 5 (7.75 ± 1.92 and 10.56 ± 1.23 mm, 5.12 ± 0.91 and 5.93 ± 1.74 mm respectively). Conclusion: Significant increase in TST sizes suggests that decongestive lymphatic therapy is able to partially restore impaired cellular immune function in BCRL.
Article
To quantitate visual findings in lymphoscintigraphy with 99mTc-labeled stannous sulfur colloids, a numeric index of transport kinetics was designed by combining visual assessment of five criteria: temporal and spatial distribution of the radionuclide, appearance time of lymph nodes, and graded visualization of lymph nodes and vessels. For assessment, scores were used ranging from 0 to 9. Thus, the resulting transport index (TI) ranged from 0 (normal) to 45 (pathological). TI in healthy extremities was less than 10. Lymphoscintigraphy was performed routinely in healthy lower extremities to ensure normal drainage before transplantation. In 122 investigations of upper and lower extremities, TI was found to be very sensitive (97.4%). Specificity was 90.3%. An interobserver study in 179 investigations revealed a high correlation (r=0.96). A total of 23 patients underwent autologous lymphatic transplantation. The average decrease of TI was 5.9: 31.1 before and 25.2 after transplantation. This decrease of TI was correlated with a marked decrease of the volumes of the extremities (from 3423 ml to 2580 ml). Changes in TI and volume were significant (p0.05). This method of evaluation has proved to be very sensitive, reproducible, and able to measure the transport capacity of only two or three transplanted lymph collectors.
Article
Lymphaticovenous anastomosis has been used for patients with peripheral lymphedema. However, the efficacy of this procedure is controversial due to a lack of evidence regarding postoperative patency. We sought to determine midterm postoperative patency of lymphaticovenous side-to-end anastomoses (LVSEAs) using indocyanine green fluorescence lymphography. This was a retrospective observational study set in a teaching hospital. Of 107 patients with chronic lymphedema who underwent 472 LVSEAs, 57 (223 anastomoses) consented to fluorescence lymphography and comprised the study cohort. The intervention consisted of a microsurgical LVSEA performed with a suture-stent method. Patients also had preoperative and postoperative complex decongestive physiotherapy. Anastomosis patency was assessed using indocyanine green fluorescence lymphography ≥6 months after surgery. Patency rates were calculated using Kaplan-Meier analysis. We assessed volume reduction on the operated-on limb and compared this between patients in whom anastomoses were patent and those in whom anastomoses were not obviously patent. Patency could be evaluated only at the dorsum of the foot, ankle, and lower leg because the near-infrared rays emitted by the special camera used could not penetrate the deep subcutaneous layer containing collective lymphatics in areas such as the thigh. Several patterns were observed on fluorescence lymphography: straight, radial, and L-shaped. Cumulative patency rates of LVSEAs were 75% at 12 months and 36% at 24 months after surgery. No significant difference in volume change of the affected limb was seen between the 34 patients with patent anastomosis (600 ± 969 mL) and the 24 patients without obvious evidence of patency (420 ± 874 mL). Although further study is required to determine factors leading to anastomotic obstruction and to optimize the results of microlymphatic surgery, the present LVSEA technique appears promising.
Article
The lymphatic system is not only essential for maintenance of normal fluid balance, but also for proper immunologic function by providing an extensive network of vessels, important for cell trafficking and antigen delivery, as well as an exclusive environment, the lymph node (LN), where antigen-presenting cells (APCs) and lymphocytes can encounter and interact. Among APCs, dendritic cells (DCs) have a remarkable capacity to traffic from peripheral tissues to the draining LN, which is critical for execution of their functions. To reach the LN, DCs must migrate towards and enter lymphatic vessels. Here, the authors review what is known about the factors that drive this process. They touch particularly on the topic of how DC migration is affected by inflammation and discuss this in the context of lymphatic function. Traditionally, inflammatory mediators are regarded to support DC migration to LNs because they induce molecules on DCs known to guide them to lymphatics. The authors recently showed that inflammatory signals present in a strong vaccine adjuvant induce swelling in LNs accompanied by lymphangiogenesis in the draining LN and radius of peripheral tissue. These increased lymphatics, at least for several days, lead to a more robust migration of DCs. However, the density of lymphatic vessels can become overly extended and/or their function impaired as observed during lymphedema and various chronic inflammatory reactions. Diseases characterized by chronic inflammation often present with impaired DC migration and adaptive immunity. Gaining a better understanding of how lymphatic vessel function may impact adaptive immunity by, for example, altering DC migration will benefit clinical research aiming to manipulate immune responses and manage chronic inflammatory diseases.
Article
To prospectively assess the efficacy of the lymphatic microsurgical preventive healing approach (LYMPHA) to prevent lymphedema after axillary dissection (AD) for breast cancer treatment. 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. 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). LYMPHA represents a valid technique for primary prevention of secondary arm lymphedema with no risk of leaving undetected malignant disease in the axilla.
Article
The lymphatics began receiving attention in the scientific community as early as 1622, when Gasparo Aselli noted the appearance of milky-white vessels in the mesentery of a well-fed dog. Since this time, the lymphatic system has been historically regarded as the sewer of the vasculature, passively draining fluid and proteins from the interstitial spaces (along with lipid from the gut) into the blood. Recent reports, however, suggest that the lymphatic role in lipid transport is an active and intricate process, and that when lymphatic function is compromised, there are systemic consequences to lipid metabolism and transport. This review highlights these recent findings, and suggests future directions for understanding the interplay between lymphatic and lipid biology in health and disease.
Article
To report the wide clinical experience and the research studies in the microsurgical treatment of peripheral lymphedema. 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. 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. 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.
Article
Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling--predominantly collagen and fat deposition--may dictate tissue swelling and govern interstitial transport in lymphedema.
Article
Adipose tissue is an endocrine organ made up of adipocytes, various stromal cells, resident and infiltrating immune cells, and an extensive endothelial network. Adipose secretory products, collectively referred to as adipokines, have been identified as contributors to the negative consequences of adipose tissue expansion that include cardiovascular disease, diabetes and cancer. Systemic blood circulation provides transport capabilities for adipokines and fuels for proper adipose tissue function. Adipose tissue microcirculation is heavily impacted by adipose tissue expansion, some adipokines can induce endothelial dysfunction, and angiogenesis is necessary to counter hypoxia arising as a result of tissue expansion. Tumors, such as invasive lesions in the mammary gland, co-opt the adipose tissue microvasculature for local growth and metastatic spread. Lymphatic circulation, an area that has received little metabolic attention, provides an important route for dietary and peripheral lipid transport. We review adipose circulation as a whole and focus on the established and potential interplay between adipose tissue and the microvascular endothelium.
Article
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. 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. 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. 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.
Article
The role of microvascular surgery in replantation and reconstruction is established. Careful case selection is emphasized and there is a need for restructuring surgical units to incorporate this development. Many tissues can be transferred with the aid of microvascular surgery, including free muscle transplant and large bone grafts, which we are actively investigating at experimental and clinical levels. Further, the application to clinical allograft transplantation is not far distant. Microvascular surgery has had a brief yesterday, for it is the surgery of today and certainly of tomorrow.
Article
According to an embryological basis, the Authors analyze the development of the vascular system and try to establish a differentiation between angiodysplasias and abnormalities. They define the characteristics of each group and make an attempt at classification. The major characteristics of differentiation are the evolutional aspects and the presence of arteriovenous fistulas.
Article
The efficacy of transferring vascularised lymph nodes into lymphoedematous limbs was investigated. Stable below-knee lymphoedema was established in one hind limb of 10 dogs. The superficial inguinal lymph node and perinodal tissue from the normal hind limb was moved to the popliteal region of the lymphoedematous leg as a free vascularised transfer. In five dogs lymphaticolymphatic anastomoses between lymphatics of the node and proximal recipient site lymphatics were also performed. Circumferential measurements of the foot, ankle and midleg were obtained preoperatively and postoperatively at 3 and 6 months. These measurements showed postoperative reduction of the lymphoedematous legs compared to controls, with no added benefit from lymphaticolymphatic anastomoses. Technetium 99 scans and lymphangiography demonstrated re-establishment of lymphatic continuity in all recipient legs at 3 and 6 months post-transfer. Histological examination at 3 and 6 months revealed normal architecture in 9 of 10 nodes, although areas of lymphocyte depletion were common. Vascularised lymph node transfer to a lymphoedematous leg re-established lymphatic continuity and resulted in partial reduction of limb size. The addition of lymphaticolymphatic anastomosis to vascularized node transfer is neither necessary nor beneficial.
Article
Lymph stasis in the extremities caused by interruption of lymphatics or insufficient lymph propulsion is often complicated by recurrent skin infections. To shed further light on this subject, we studied the phenotypical and functional characteristics of cells in peripheral lymph and skin of patients with obstructive lymphedema. Compared with controls, patients with secondary lymphedema displayed a high concentration of lymphocytes and erythrocytes in peripheral lymph, sometimes increased numbers of B cells, increased density of Langerhans cells in the epidermis and occasionally in the skin papillary layer, strong expression of class II antigens on skin endothelial cells and mononuclear infiltration around blood vessels, and margination of granulocytes in skin blood vessels. Reactivity of lymph cells to mitogens was augmented. Taken together these findings indicate that ongoing chronic inflammatory processes persist in skin with lymph stasis, and, moreover, with impaired lymphocyte and Langerhans cell trafficking from skin to regional lymph nodes and inefficient clearance of foreign antigens, these lymphedematous limbs become susceptible to infection.
Article
Our clinical observations in 64 patients affected by chronic obstructive lymphedema (either arm or leg) undergoing interposition autologous lymphatic- venous-lymphatic (LVL) anastomoses are reported. This microsurgical technique is an alternative to other lymphatic shunting methods, especially when venous dysfunction coexists in the same limb and, therefore, when direct lymphatic- venous anastomosis is accordingly inadequate. Preoperative diagnostic evaluation (including lymphatic and venous isotopic scintigraphy, Doppler venous flowmetrics, and pressure manometry) plays an essential role in assessing the conditions of both the lymphatic and venous systems and in establishing which microsurgical procedure, if any, is indicated. Our microsurgical technique consists of inserting suitably large and lengthy autologous venous grafts between lymphatic collectors above and below the site of obstruction to lymph flow. The data show that, using this technique, both limb function and edema improved, and in all patients followed up for over 5 years edema regression was permanent.
Article
Microsurgical lymphaticovenous anastomoses were done on a total of 14 patients. Six upper extremities of six female patients (average age 56.5 years) were operated on with lymphaticovenous anastomoses and were followed up for 17 months or more after surgery (average 25.5 months). Twelve legs of eight patients (average age 44.6 years) also were operated on and followed up for 12 months or more after surgery (average 23.4 months). Among these patients, 33 biopsied lymphatic trunks with lymphedema in 16 extremities of 12 patients were evaluated histologically by light and electron microscopy. Regarding the operative effect in the arms, the decreased circumference of the arms ranged from 2 to 9 cm (average 5.3 cm). The rate of preoperative versus postoperative excess circumference decreased in range from 25 to 94.7 percent (average 65.7 percent). As for the surgical effect in the legs, half the legs showed improvement. These postoperative improvements showed no correlation with the preoperative duration of edema and excess circumference in either the upper or lower extremities. Histologically, in the initial stage of lymphedema, there was destruction of both endothelial cells and smooth muscle cells in the proximal level of the lymphatic trunks. The lumen of some proximal trunks was then occluded by organization with a few small recanalizations, but the distal lymphatics remained patent with minimal destruction of both the endothelial cells and the smooth muscle cells even in the later stage of lymphedema. These results suggest that the occlusions of the lymphatic trunks and degeneration of the smooth muscle cells may start from the proximal ends of the extremities and that the timing of the occlusions and the degeneration of smooth muscle cells may not correspond to the duration of edema. It is also considered that because of the smooth muscle degeneration, the lymph-drainage capacity of the lymphatic trunks may be remarkably weakened in the proximal lymphatics of the extremities. Therefore, it is suggested that the remaining lymphatic drainage function with the smooth muscle cells may correlate with the postoperative improvement of edema. It is also suggested that the preoperative ultrastructural examination of the lymph-drainage capacity may be a suitable method for predicting the surgical effect and operative indication for lymphatic edema in the extremities.
Article
Over the last 9 years, the authors analyzed lymphedema of the lower extremity in a total of 25 patients, comparing the use of supermicrosurgical lymphaticovenular anastomosis and/or conservative treatment. The most common cause of edema was hysterectomy, with or without subsequent radiation therapy for uterine cancer. Among 12 cases that underwent only conservative treatment, only one case showed a decrease of over 4 cm in the circumference of the lower leg. The average period for conservative treatment was 1.5 years, and the average decreased circumference was 0.6 cm (8 percent of the preoperative excess). Thirteen patients were followed after lymphaticovenular anastomoses, as well as pre- and postoperative conservative treatment. The average follow-up after surgery was 3.3 years, and eight patients showed a reduction of over 4 cm in the circumference of the lower leg. The average decrease in the circumference, excluding edema in the bilateral leg, was 4.7 cm (55.6 percent of the preoperative excess). These results indicate that supermicrosurgical lymphaticovenular anastomosis has a valuable place in the treatment of lymphedema.
Article
We analyzed clinicopathologic and imaging features of chronic peripheral lymphedema to identify imaging findings indicative of its exact etiopathogenesis and to establish the optimal treatment strategy. One of the main problems of microsurgery for lymphedema is the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic studies and surgical outcome have not been adequately documented. Over the past 25 years, 676 patients with peripheral lymphedema have been treated with microsurgical lymphatic-venous anastomoses. Of these patients, 447 (66%) were available for long-term follow-up study. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Objectively, volume changes showed a significant improvement in 561 patients (83%), with an average reduction of 67% of the excess volume. Of the 447 patients followed, 380 (85%) have been able to discontinue the use of conservative measures, with an average follow-up of more than 7 years and average reduction in excess volume of 69%. There was an 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical lymphatic-venous anastomoses 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. Improved results can be expected with operations performed early, during the first stages of lymphedema.
Article
The efficient function of the immune system necessitates the complex interaction of antigens, antigen-presenting cells, and cell populations that modulate, regulate and effectuate the immune response. In order to overcome the spatial limitations that are imposed by the constraints of the system, the immune system has evolved a dependence upon the lymphatic vasculature to serve the biological needs of immune trafficking. This review will focus upon useful ex vivo and intact animal models that possess the ability to provide valuable information about leukocyte trafficking.
Article
Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis and holds potential for lymphangiogenic therapy in diseases lacking adequate lymphatic drainage. However, the ability of VEGF-C to enhance sustainable, functional lymphatic growth in adult tissues remains unclear. To address this, we evaluated VEGF-C overexpression in adult lymphangiogenesis in regenerating skin. We used a model of mouse tail skin regeneration incorporating a suspension of either VEGF-C overexpressing tumor cells, which provide a continuous supplement of excess VEGF-C to the natural regenerating environment for more than 25 days, or otherwise identical control-transfected tumor cells. We found that excess VEGF-C did not enhance the rate of lymphatic endothelial cell (LEC) migration, the density of lymphatic vessels, or the rate of functionality -- even though lymphatic hyperplasia was present early on. Furthermore, the hyperplasia disappeared when VEGF-C levels diminished, which occurred after 25 days, rendering the lymphatics indistinguishable from those in control groups. In vitro, we showed that whereas cell-derived VEGF-C could induce chemoattraction of LECs across a membrane (which involves amoeboid-like transmigration), it did not increase LEC chemoinvasion within a 3-dimensional fibrin matrix (which requires proteolytic migration). These results suggest that whereas excess VEGF-C may enhance early LEC proliferation and cause lymphatic vessel hyperplasia, it does not augment the physiological rate of migration or functionality, and by itself cannot sustain any lasting effects on lymphatic size, density, or organization in regenerating adult skin.