Background: Lymphedema is a chronic, debilitating condition that has traditionally been seen as refractory or incurable. Recent years have brought new advances in the study of lymphedema pathophysiology. as well as diagnostic and therapeutic tools that are changing this perspective. Objective: To provide a systematic approach to evaluating and managing patients with lymphedema. Methods: We performed MEDLINE searches of the English-language literature (1966 to March 2006) using the terms lymphedema, breast cancer-associated lymphedema, lymphatic complications, lymphatic imaging, decongestive therapy, and surgical treatment of lymphedema. Relevant bibliographies and International Society of Lymphology guidelines were also reviewed. Results: In the United States, the populations primarily affected by lymphedema are patients undergoing treatment of malignancy, particularly women treated for breast cancer. A thorough evaluation of patients presenting with extremity swelling should include identification of prior surgical or radiation therapy for malignancy, as well as documentation of other risk factors for lymphedema, such as prior trauma to or infection of the affected limb. Physical examination should focus on differentiating signs of lymphedema from other causes of systemic or localized swelling. Lymphatic dysfunction can be visualized through lymphoscintigraphy; the diagnosis of lymphedema can also be confirmed through other imaging modalities, including CT or MRI. The mainstay of therapy in diagnosed cases of lymphedema involves compression garment use, as well as intensive bandaging and lymphatic massage. For patients who are unresponsive to conservative therapy; several surgical options with varied proven efficacies have been used in appropriate candidates, including excisional approaches, microsurgical lymphatic anastomoses, and circumferential suction-assisted lipectomy, an approach that has shown promise for long-term relief of symptoms. Conclusions: The diagnosis of lymphedema requires careful attention to patient risk factors and specific findings on physical examination. Noninvasive diagnostic tools and lymphatic imaging can be helpful to confirm the diagnosis of lymphedema or to address a challenging clinical presentation. Initial treatment with decongestive lymphatic therapy can provide significant improvement in patient symptoms and volume reduction of edematous extremities. Selected patients who are unresponsive to conservative therapy can achieve similar outcomes with surgical intervention, most promisingly suction-assisted lipectomy. (Less)

Lymphedema: a comprehensive review.

Lymphedema-edema that results from chronic lymphatic insufficiency-is a chronic debilitating disease that is frequently misdiagnosed, treated too late, or not treated at all. There are, however, effective therapies for lymphedema that can be implemented, particularly after the disorder is properly diagnosed and characterized with lymphoscintigraphy. On the basis of the lymphoscintigraphic image pattern, it is often possible to determine whether the limb swelling is due to lymphedema and, if so, whether compression garments, massage, or surgery is indicated. Effective use of lymphoscintigraphy to plan therapy requires an understanding of the pathophysiology of lymphedema and the influence of technical factors such as selection of the radiopharmaceutical, imaging times after injection, and patient activity after injection on the images. In addition to reviewing the anatomy and physiology of the lymphatic system, we review physiologic principles of lymphatic imaging with lymphoscintigraphy, discuss different qualitative and quantitative lymphoscintigraphic techniques and their clinical applications, and present clinical cases depicting typical lymphoscintigraphic findings.

https://jnm.snmjournals.org/content/jnumed/44/1/43.full.pdf

Who is at risk for developing chronic anal fistula or recurrent anal sepsis after initial perianal abscess

Background:The authors prospectively evaluated the efficacy of lymphovenous bypass in patients with lymphedema secondary to cancer treatmentMethods:The authors prospectively enrolled 100 consecutive patients with extremity lymphedema secondary to cancer treatment Sixty-five patients underwent lymp

A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema.

The differentiation of fibroblasts to contractile myofibroblasts, which is characterized by de novo expression of alpha-smooth muscle actin (alpha-SMA), is crucial for wound healing and a hallmark of tissue scarring and fibrosis. These processes often follow inflammatory events, particularly in soft tissues such as skin, lung and liver. Although inflammatory cells and damaged epithelium can release transforming growth factor beta1 (TGF-beta1), which largely mediates myofibroblast differentiation, the biophysical environment of inflammation and tissue regeneration, namely increased interstitial flow owing to vessel hyperpermeability and/or angiogenesis, may also play a role. We demonstrate that low levels of interstitial (3D) flow induce fibroblast-to-myofibroblast differentiation as well as collagen alignment and fibroblast proliferation, all in the absence of exogenous mediators. These effects were associated with TGF-beta1 induction, and could be eliminated with TGF-beta1 blocking antibodies. Furthermore, alpha1beta1 integrin was seen to play an important role in the specific response to flow, as its inhibition prevented fibroblast differentiation and subsequent collagen alignment but did not block their ability to contract the gel in a separate floating gel assay. This study suggests that the biophysical environment that often precedes fibrosis, such as swelling, increased microvascular permeability and increased lymphatic drainage--all which involve interstitial fluid flow--may itself play an important role in fibrogenesis.

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Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro

Background:Indocyanine green lymphography has been a highly useful modality in the clinical examination and surgical management of patients with lymphedema. No formal classification system of indocyanine green imaging findings according to the severity of lymphedema exists, however. The purpose of t

Characteristic Indocyanine Green Lymphography Findings in Lower Extremity Lymphedema: The Generation of a Novel Lymphedema Severity Staging System Using Dermal Backflow Patterns

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. V C 2010 Wiley-Liss, Inc. Microsurgery 30:256‐260, 2010. Lymphedema, refractory to nonoperative methods, may be managed by surgical treatment. Indications include insufficient lymphedema reduction by well performed medical and physical therapy (less than 50%), recurrent episodes of lymphangitis, intractable pain, worsening limb function, patient unsatisfied of the result obtained by nonoperative methods and willing to proceed with surgical options. The first microsurgical derivative operations were those using lymphnodal-venous shunts. These have been largely abandoned, except in endemic areas of lymphatic filariasis such as India where thousands of these procedures have been performed. Lymphatic channels in lymphnodal-venous anastomoses are often widely dilated due to the high rate of anastomotic closures caused by the thrombogenic effect of lymph nodal pulp on the venous blood and the frequent re-endothelization of the lymph nodal surface. 1 Because of the difficulties encountered with lymphnodal-venous shunts by surgeons worldwide, the next approach was to use lymphatic vessels directly anastomosed to veins. 2 The technique consists in anastomosing lymphatic vessels to a collateral branch of the main vein, checking the perfect function of the valvular apparatus, to be sure of the correct continence of the vein segment used for the anastomosis. This way, inside the venous tract there flows only lymph and not blood, avoiding any risk of thrombosis of anastomosis. 3 The retrospective evaluation of our wide clinical experience in the microsurgical treatment of peripheral lymphedema is reported, underlying long term outcome and analyzing which are the correct indications and technical details that allow us to obtain successful results long term after operation.

Microsurgery for lymphedema: Clinical research and long‐term results

Background
The purpose of this manuscript is to assess the efficacy of direct lymphaticvenous microsurgery in the prevention of lymphedema following axillary dissection for breast cancer.

Lymphedema Microsurgical Preventive Healing Approach: A New Technique for Primary Prevention of Arm Lymphedema After Mastectomy

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.

Microsurgical techniques for lymphedema treatment: derivative lymphatic-venous microsurgery.

One of the main problems of microsurgery for lymphedema consists of the discrepancy between the excellent technical possibilities and the subsequently insufficient reduction of the lymphoedematous tissue fibrosis and sclerosis. Appropriate treatment based on pathologic study and surgical outcome have not been adequately documented. Over the past 25 years, more than 1000 patients with peripheral lymphedema have been treated with microsurgical techniques. Derivative lymphatic micro-vascular procedures has today its most exemplary application in multiple lymphatic-venous anastomoses (LVA). For those cases where a venous disease is associated to more or less latent or manifest lymphostatic pathology of such severity to contraindicate a lymphatic-venous shunt, reconstructive lymphatic microsurgery techniques have been developed (autologous venous grafts or lymphatic-venous-Iymphatic-plasty - LVLA). 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 7 years and average reduction in excess volume of 69%. There was a 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 earlier at the very first stages of lymphedema. © 2006 Wiley-Liss, Inc. Microsurgery 26: 65–69, 2006.

Lymphatic microsurgery for the treatment of lymphedema.

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.

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Corradino Campisi

Papers

Microsurgery for lymphedema: Clinical research and long‐term results

Lymphedema Microsurgical Preventive Healing Approach: A New Technique for Primary Prevention of Arm Lymphedema After Mastectomy

Microsurgical techniques for lymphedema treatment: derivative lymphatic-venous microsurgery.

Lymphatic microsurgery for the treatment of lymphedema.

Surgical prevention of arm lymphedema after breast cancer treatment.