Surgical procedures in lymphedema management

Surgical procedures in lymphedema management

Surgical procedures in lymphedema management Catarina Hadamitzky, MD,a Reinhard Pabst, MD,b Kristiana Gordon, MD,c and Peter M. Vogt, MD,a Hannover, G...

461KB Sizes 17 Downloads 237 Views

Surgical procedures in lymphedema management Catarina Hadamitzky, MD,a Reinhard Pabst, MD,b Kristiana Gordon, MD,c and Peter M. Vogt, MD,a Hannover, Germany; and London, United Kingdom Objective: Lymphedema has a high incidence and various causes. It reduces patients’ quality of life and productivity and currently lacks a cure. Management is based on lifelong physical therapies. Many surgical procedures have been proposed for lymphedema without significant acceptance. This study evaluates surgical procedures aimed at the management of lymphedema and highlights present evidence. Methods: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Grading of Recommendations Assessment, Development and Evaluation consensus, a systematic literature search (MEDLINE and The Cochrane Library) was performed to identify studies evaluating treatment outcomes after lymphedema surgery. The authors evaluated all articles found with the keywords “lymphedema” and “surgery,” including experimental studies in animals. Cross referencing was made. Next, a protocol was created to assess the degree of quality of publications in this field. An overview of the complete medical literature was performed. Thereafter, publications meeting inclusion criteria were attributed a score according to the assessment protocol. This allowed an

overview of the scientific quality of all surgical procedures for lymphedema. Results: A total of 108 article texts were read and 70 publications included in this study according to predefined criteria. Lymphedema operative procedures were classified according to type. The outcomes highlighted the importance of individual patient analysis, as most interventions are not sufficiently studied to sustain clinical recommendations. Conclusions: Risk factors for acquired lymphedema, such as lymph node excision and radiation therapy, are well identified and should allow primary prevention. Improved diagnosis, classification, standardized volume measurement, staging, and follow-up of lymphedema patients can facilitate their management and allow valid retrospective studies. Currently, there is no evidence of any treatment yielding high long-term cure rates. Therefore, lymphedema management must be based on interdisciplinary approaches, with curative or palliative therapy options discussed openly with the patient. Therapeutic plans should not exclude surgery. Nevertheless, additional studies are recommended to prove the validity of some surgical approaches. (J Vasc Surg: Venous and Lym Dis 2014;-:1-8.)

Lymphedema is the pathologic accumulation of lymphatic fluid within the tissue. It occurs when lymphatic transport fails to drain the capillary filtrate, proteins, isolated cells, debris, and pathogens present in the peripheral intercellular space. The difficulties encountered in the anatomic preparation of transparent lymphatic vessels and in the research on the complex physiology of lymphatic transport and the absence of curative therapies for lymphatic diseases have contributed to the neglect of this specialty by the medical community. Currently, lymphedema management

is mainly performed by physiotherapists in the form of lifelong palliative manual lymphatic drainage, compression garments, skin care, and exercise. This condition constitutes a major health problem worldwide because of its high prevalence and costs of lifelong health care resources. It may be congenital or acquired, the latter having a higher incidence. Causes of acquired lymphedema vary worldwide. In developing countries, it may be due to podoconiosis, but it mainly occurs through infection with filaria worms. According to World Health Organization data, patients presenting with lymphedema caused by filarial infection number 40 million cases worldwide.1 In developed countries, acquired lymphedema mainly occurs as a result of oncologic surgery when draining lymph nodes have to be removed or irradiated to avoid spread of the tumor (eg, in breast cancer, pelvic cancers, and melanoma). Other causes include burns, trauma, and infection. The prevalence of lymphedema in developed countries is not known. Its incidence after cancer surgery with lymphadenectomy or radiation therapy affects up to 30% of patients.2 However, the incidence is lower for procedures involving only sentinel lymph node biopsy and higher for those patients undergoing radiation therapy.2 Because of the large number of patients affected by lymphedema, efforts have been made to find new therapies for this condition. Many surgical procedures have been proposed over the years. The objective of this study was to analyze existing data and to assess surgical long-term

From the Department of Plastic, Hand and Reconstructive Surgery (Director: Univ.-Prof. Dr. med. Peter M. Vogt)a and Institute of Immunomorphology,b Hannover Medical School, Hannover; and the Dermatology Department, St George’s Hospital, London.c This study was partially supported by the Lifelong Learning Projects of the European Union 142736-LLP-1-2008-1-DE-ERASMUS-ECDSP and 527658-LLP-1-2012-1-DE-ERASMUS-ESMO), by a grant of the Hannover Medical School (Habilitationsförderung), and by a British Heart Foundation grant (FS/11/40/28739). Author conflict of interest: none. Reprint requests: Dr med. Catarina Hadamitzky, Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany (e-mail: hadamitzky. [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 2213-333X/$36.00 Copyright Ó 2014 by the Society for Vascular Surgery. http://dx.doi.org/10.1016/j.jvsv.2014.02.001

1

2 Hadamitzky et al

JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS --- 2014

results. In addition, concepts arising from the search for surgical solutions provide interesting insights into what possibilities lay unexplored that could eventually provide a cure for this disease. METHODS A systematic literature search was conducted with validated methods of the Cochrane Collaboration. The search strategy for MEDLINE (PubMed) was based on the search algorithm presented in Table I. The last search was carried out in November 2013. Searched databases included MEDLINE and The Cochrane Library. The search was restricted to articles in English, French, Spanish, Portuguese, German, and Italian. A meta-analysis was not possible because of marked disparity in study populations, evaluation criteria, and volume measurement methods. Publications were selected that referred to surgical methods aimed at treatment of lymphedema of the limbs. Animal studies were included. Surgical methods to treat lymphedema of the trunk, genitals, or head and neck region were excluded. Trials concerning surgical techniques aiming for lymphedema prevention, analyzing lymphedema incidence, or not directly connected to the objectives of this study were excluded. Single-case studies were also excluded. Included studies were compiled into five categories: (1) excisional or “debulking” methods; (2) liposuction techniques; (3) anastomosis between the lymphatic and the venous system; (4) lympholymphatic anastomosis or lympholymphatic vessel interpositions; and (5) lymph node transplantation or lymphatic tissue flaps. Each of these categories were separately analyzed for reported success rates, operative indications, and recommendations as well as for quality of the evidence presented. According to the Grading of Recommendations Assessment, Development and Evaluation system,3 the majority of considered publications sustained “low” to “very low” evidence for guideline recommendations. However, to facilitate a differentiation within the low spectrum of evidence of research publications in this field of medicine, a score was developed by the authors. The criteria of the score are listed in Table II. Table I. Search algorithm for PubMed (MEDLINE) Search: Lymph*edema surgery Limits Activated: only items with links to full text, Clinical Trial, Editorial, Meta-Analysis, Practice Guideline, Randomized Controlled Trial, Review, Classical Article, Clinical Conference, Clinical Trial, Phase I, Clinical Trial, Phase II, Clinical Trial, Phase III, Clinical Trial, Phase IV, Comparative Study, Consensus Development Conference, Consensus Development Conference, NIH, Controlled Clinical Trial, Corrected and Republished Article, Duplicate Publication, Evaluation Studies, Government Publications, Guideline, Historical Article, Introductory Journal Article, Journal Article, Lectures, Multicenter Study, Scientific Integrity Review, Twin Study, Validation Studies.

Table II. Quality assessment score used Quality assessment score for trials on lymphedema surgery

Points

Prospective study Clear study protocol Consistent study population with explicit lymphedema grading Statistical analysis mentioning standard deviation and confidence intervals Follow-up longer than 1 year and stated with standard deviation Specification of adjuvant therapy before and after surgery (type, duration, frequency), eg, manual lymphatic drainage Serial lymphedema measurement with reliable methods, with intraindividual or interindividual control Standardization and clear description of the surgical technique Postoperative assessment of results through direct imaging of lymphatics Reports on serious complications, such as infections, fistula, and wounds Total

1 1 1 1 1 1 1 1 1 1 10

RESULTS Of 1778 citations, 70 publications met the inclusion criteria. The Fig demonstrates the selection process of publications according to the different categories. All included publications were published in peer-reviewed journals. Study quality. Considerable heterogeneity with regard to methodologic quality was observed throughout all study categories. In addition, some publications included overlapping clinical populations repeatedly analyzed retrospectively by the same authors. With regard to excisional or debulking methods, only four MEDLINE quoted publications exist. The quality of these studies according to our protocol was poor, with an average quality score of 3.5. Liposuction techniques were described in seven original articles.eg4-6 These studies presented a good level of evidence according to our criteria, with an average quality score of 6.3. Publications on lymphovenous anastomosis (LVA) outnumbered other interventions with a total of 31 papers.eg7-9,10-21 Nevertheless, they also presented the widest range of quality. Most publications in this category offered a low score, with an average of 3.8. Studies on lympholymphatic anastomosis were numerouseg22,23 and had a good level of quality with an average score of 5.8. Studies on lymph node transplantation24,25,eg26 or flaps including lymphatic tissue27-34 attained a relatively low average score of 6.1. An average quality score of all publications according to the category is presented in Table III. Reviews were all purely descriptive of the surgical techniques without analysis of the quality of reported publications,35,36 with the exception of one.37 These articles were excluded from the qualitative analysis.

JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS Volume -, Number -

Fig. Publication selection process.

Historical overview of surgical procedures for lymphedema. When the French anatomist Sappey published his studies visualizing cadaver lymphatics with mercury in 1874, the existence of both deep and superficial lymphatic drainage systems was made public. On the basis

Hadamitzky et al 3

of his observations, Sappey erroneously postulated that these two systems were not connected, motivating highly ineffective surgical connection attempts for the centuries that followed. Radical excisions. After his voyages to India, Sir Charles published his series of operations for scrotal lymphedema in 1912. His operation consisted of a massive resection of scrotal and penile skin and subcutaneous tissue. The penis was covered with a circular autologous full-thickness skin graft. Charles mentioned the possibility of operating on lymphedematous legs through complete resection of the skin and subcutaneous tissue and replacing the skin in its full length by a skin graft, but he did not report having performed the lower limb operation in a single patient. In 1950, he was misquoted by McIndoe for having treated patients with lymphedema of the lower limbs. This was permanently reiterated until it became of general acceptance to name the “Charles procedure” after a surgeon who never performed it! Because of reported problems of necrosis of the skin transplant, the concept of tissue resection and local skin grafts in lymphedema of the limbs is currently restricted to local treatment of resistant fibrosis and chronic wounds. Liposuction instead of lipectomy. The principle behind the use of liposuction in lymphedema is derived from excisional methods but has the advantage of preventing extensive wounds. Although it is purely palliative, liposuction permits an effective volume reduction in therapy-resistant lymphedema of the extremities. Nevertheless, this therapy should be used exclusively in compliant patients willing to permanently wear lifelong compression garments. As soon as patients disregard regular use of garments, they suffer a relapse or worsening of lymphedema.36 Liposuction may cause injury to remaining subcutaneous lymphatics within lymphedematous extremities. This injury can be minimized with use of a specific technique. Wet liposuction cannulas inserted exclusively in the longitudinal direction cause less injury than suction transversal to the axis of the extremity.38 Surgical approaches to improvement or reconstruction of lymphatic drainage. Another branch of lymphedema surgery focuses on concepts aimed at the correction of lymphedema through improvement or reconstruction of lymphatic drainage.

Table III. Quality score overview of publications in each category Category Excisional or “debulking” methods Liposuction techniques Lymphatic and venous system anastomosis Lympholymphatic anastomosis or vessel interpositions Lymph node transplantation or flaps including lymphatic tissue

No. of publications No. of research groups involved Average quality score Range 4 7 31 10 12

4 2 14 1 6

3.5 6.3 3.8 5.8 6.1

1-6 4-8 1-9 5-7 2-7

Publications were considered from one single research group when they had at least one author in common and this author was first or senior author of at least one publication of the group. The maximum score of 100 points was attained by no reviewed publication. A score of 0 points corresponds to low quality and low level of evidence.

4 Hadamitzky et al

JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS --- 2014

Anastomosis between lymphatics and veins. In the process of discovering operative solutions for the resolution of lymphedema, surgeons attempted to anastomose lymph nodes and veins. Nielubowicz and Olsewski began their series in the 1960s and included pediatric patients with primary and secondary lymphedema. Unfortunately, their results were very poor. Microsurgery of lymphatics and veins. With the development of microsurgical procedures, a new world of possibilities opened to surgeons. Microsurgical LVAs were first described by Degni and Cordeiro35 and corresponded to two to five terminal-lateral anastomoses between lymphatic collectors and superficial veins. The procedure has since developed a relative popularity because of its minimal invasiveness (small incisions) and short hospital stay, rendering it financially attractive. O’Brien et al37 retrospectively described patients operated on with end-to-side anastomosis. Their average follow-up was 18.6 months; 21 patients had an average volume reduction of 32%, and 14 patients had a volume increase of 18%. In spite of these ambiguous results, this therapeutic option was still recommended by the authors. Filippetti et al14 described in their series of 25 patients “good” results in all subjects. However, no volumetric values were included in the follow-up, and only subjective criteria were analyzed. In addition, patients were included in this study who had developed lymphedema in the previous 4 months, thus not fulfilling the necessary criteria for the exclusion of a spontaneous remission. Retrospective studies that include the largest numbers of patients are those of Campisi et al,eg7-9 who have performed LVA procedures on thousands of patients. In their retrospective series, they included heterogeneous causes of lymphedema and patients with disparate follow-ups. Lymphoscintigraphy was not performed in all patients, and patency rates of the performed anastomosis were not given. Most patients were Campisi grades 1 and 2 (corresponding to stage I of the International Society of Lymphology). Some were operated on with end-to-end LVAs, and some with end-to-side LVAs. With the use of end-to-end anastomosis, the authors described many complications, including venous reflux and thrombosis, but still recommended the procedure in their discussion. An overview of their results is difficult to obtain because quantified results vary from the tables and the publication text. Success rate was reportedly 83% of the patients (>1800 patients in some series), but the improvement criteria are not mentioned. One prospective study of LVAs from Vignes et al20 analyzed 13 patients with arm and leg lymphedema (10 primary, three secondary) submitted to two to five anastomoses. Follow-up was 52  3 months. The difference between the preoperative and postoperative volume measurements was not statistically significant. There was no significant decrease of the number of erysipelas episodes. Subjectively, patients reported a significant decrease in the sensation of tension in the limb, this being the only parameter to have changed as a result of the operation.

Supermicroanastomosis of lymphatic capillaries and venules. In the last decades, improvement of microsurgical equipment allowed the development of supermicrosurgery techniques.17 These aim at the anastomosis of vessels at the capillary level with a diameter of 0.8 to 0.3 mm. An overview of relevant publications on both micro-LVAs and supermicro-LVAs is given in Table IV. Publications on the outcome of supermicro-LVA procedures have a slightly higher level of quality than the ones on micro-LVAs according to our score. Nevertheless, some authorseg18 suggest no objective improvement of lymphedema volume after this procedure. A prospective study conducted by Damstra12 was performed in 10 patients with lymphedema of the arm exclusively, all resistant to traditional physical therapy. All patients were assigned to International Society of Lymphology stage II. Measurements obtained by water volumetry and lymphoscintigraphy were undertaken, as was a quality of life assessment. An average volume reduction of 4% was observed 3 months after supermicro-LVAs. The quality of life slightly improved in five patients 6 months after surgery. No significant volume reduction could be seen after 1 year, and lymphoscintigraphy showed no patency of any bypass after 12 months. Microanastomosis within the lymphatic system. The rationale of lympholymphatic anastomosis is to avoid the problems inherent to LVAs caused by coagulation of blood within the lymphatics. This technique, pioneered by Baumeister, has been used by other microsurgeons. Baumeister et aleg22,23 propose different solutions according to the impaired extremity. In arm lymphedema, two or three lymphatic vessels from the medial aspect of the thigh are transplanted to the upper arm. These transplants are anastomosed distally end to end and proximally end to side to the lymphatics descending from the jugular chain. In cases of unilateral leg lymphedema, two or three lymphatic collectors of the healthy leg are cut in the distal third of the thigh and crossed over to the groin of the lymphedematous limb. Here, anastomoses are performed end to end in the proximal third of the thigh. In his 8-year follow-up series,23 80% of the patients with arm edema showed a reduction of 22% to 27% of the excess volume and improvement of the nanocolloid transport index in lymphoscintigraphy. Volume reduction in the series for the lower extremities was 21.8%. Campisi et aleg7-9 proposed a vein interposition as lymphovenous-lymphatic anastomosis in cases of severe venous insufficiency precluding lymphatic-venous anastomosis. In their series of 95 patients (with follow-up between 10 and 15 years), a 50% to >75% reduction of lower limb lymphedema was observed in 81% of the patients, although patients with lymphedema stage I showed greater improvement than high-grade lymphedema patients did. In the long-term follow-up, only seven patients had a stabilization of their leg volume; the remaining results were not mentioned. Lymph node transplants and lymph node flaps. Autotransplantation of normal lymphatic tissue included in a local or free flap to a site deficient of lymph nodes has

JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS Volume -, Number -

Hadamitzky et al 5

Table IV. Overview of research groups publishing on anastomosis between the lymphatic and the venous system

Research group Microsurgical LVA O’Brien et al37 (1979)

No. of publications Total No. of patients and included type of lymphedema 1

Gloviczki et al15 (1988)

1

Huang et al16 (1989)

1

Filippetti et al14 (1994)

1

Campisi et al7-9 (1995-2011)

8

Yamamoto et al21 (1998)

1

Vignes et al20 (2003)

1

Matsubara et al19 (2006)

1

Supermicrosurgical LVA Koshima et aleg17,37 (1996-2013)

9

Damstra et al12 (2008)

1

Demirtas et aleg13 (20092010)

2

Chang11 (2010)

1

Maegawa et aleg18 (20112012)

2

Auba et al10 (2012)

1

Study type; assessment of results; postoperative management

30 patients; 3 upper and Retrospective; 4-point tape circumfer27 lower extremities ence measurement; postoperative management absent 14 patients; 6 upper and Retrospective; tape circumference 8 lower extremities measurement and lymphoscintigraphy; postoperative management unclear 98 patients; 7 upper and Retrospective; water displacement 91 lower extremities volumetry; well-defined postoperative management 25 patients; upper exRetrospective; subjective evaluation of tremity only results without volume measurement; postoperative management with heat therapy in some patients > 1800 patients; upper All retrospective; volumes not always and lower extremities quantified and lymphoscintigraphy not always performed; postoperative management unclear 8 patients; 5 upper and 3 Retrospective; 4-point tape circumferlower extremities ence measurement; postoperative management unclear 13 patients; 5 upper and Prospective; water displacement volu3 lower extremities metry; well-defined postoperative management 9 patients; lower exRetrospective; tape circumference tremity only measurement; postoperative management unclear > 100 patients; upper and lower extremities

All retrospective; tape circumference measurement and other methods including indocyanine green fluorescence imaging and ultrasound elastography; postoperative management not always specified 10 patients; upper exProspective; water displacement volutremity only metry and tape circumference measurement, preoperative and postoperative lymphoscintigraphy and SF-36 for quality of life quantification; well-defined postoperative management 78 patients; lower exRetrospective; tape circumference tremity only measurement; well-defined postoperative management with compression only 20 patients; upper exProspective; laser optical volumetry; tremity only well-defined postoperative management 107 patients; 22 upper Retrospective; 3-point tape circumferand 85 lower ence measurement; well-defined postoperative management extremities 10 patients; 5 upper and Retrospective; tape circumference 5 lower extremities measurement in 5-cm intervals; welldefined postoperative management

Average score

Quality of evidence (GRADE)

4

Very low

3

Very low

3

Very low

4

Very low

2.4

Very low

4

Very low

7

Low

4

Very low

3.4

Very low

9

Low

4.5

Very low

7

Low

5.5

Very low

4

Very low

GRADE, Grading of Recommendations Assessment, Development and Evaluation; LVA, lymphovenous anastomosis; SF-36, 36-Item Short Form Health Survey. Publications were considered from one single research group when they had at least one author in common and this author was first or senior author of at least one publication of the group.

6 Hadamitzky et al

JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS --- 2014

Table V. Lymphedema staging according to different authors Definition

International Society of Lymphology Campisi Filippetti

Subclinical or latent edema in which swelling is not evident despite impaired lymph transport Mild edema returning to normal after night rest Pitting edema subsiding with limb elevation Edema not changing with elevation, with tissue fibrosis that can be pitting or not (Campisi adds: ingravescent with erysipelas and cellulitis) Fibrolymphedema (initial lymphostatic verrucosis) with “column” limb Lymphostatic elephantiasis with trophic changes of the skin

0

1a

d

I

1b 2 3

I

II III

4 5

II III

Clinical stages permit a better evaluation of severity when completed with volumetric data (if possible, percentage comparison with the volume of the normal limb) and frequency of infectious episodes (cellulitis, lymphangiodermatitis). Magnetic resonance also permits a quantification of accumulated fluid in mode T2 and is especially sensitive for stage 0 lymphedema.

been used to enhance lymph transport of lymphedematous limbs. The experimental use of myocutaneous flaps containing lymph nodes was performed by Slavin et al33 on the tail lymphedema model in rodents. It was shown that acute lymphedema of the tail completely resolved after a pedicled rectus abdominis flap to the tail. Becker et al27,28 reported a series of therapy-resistant arm lymphedema patients (n ¼ 24) in which 41.6% were able to discontinue physical therapy after deep or superficial inferior epigastric perforator flap transposition to the axillary region. In addition, release of adhesions and dissection of axillary fibrotic tissue were performed. Only blood vascular anastomoses were made, no lymphatic anastomosis. In this study, 10 patients were cured of their lymphedema (41.6%), 12 patients experienced permanent volume reduction of approximately 50% of the original volume, and two patients showed no improvement. The follow-up was 5 to 12 years. Postoperative management included at least 6 months of daily lymphatic drainage without compression garments. These results were recently confirmed by other groups.29-33 Autologous lymph node transplantation, whether assimilated in a flap or not, has also been reported in animal studies. Our research group demonstrated successful regeneration of avascular autologous lymph node fragments in minipigs and rats.eg26 Tobbia et al25 transplanted vascularized lymph nodes in sheep without fragmentation and showed good regeneration rates. However, these studies involved animals without chronic lymphedema.2 Belcaro et al24 reported autologous transplantation of lymph node slices in nine patients with lower limb lymphedema. Results were characterized as good, but limb circumference increased by an average of 8% during a 10-year follow-up. In addition, the author’s use of adjuvant therapy and matching with controls remain unclear. DISCUSSION Anatomic structures associated with immunity are extremely adaptive. The regenerative capacities of lymphatic tissue have proved rewarding in reconstructive interventions. However, current operative interventions for acquired lymphedema have been unable to establish themselves within the standard therapeutic options offered

to patients. This undoubtedly is due to absence of prospective comparative studies. In addition, the guidelines of the International Society of Lymphology consider surgical interventions only in terminal cases resistant to conservative therapy, possibly leading to a condemnation of surgical success. Last, the absence of lymphedema models for surgical experiments renders therapeutic evaluation difficult.2 Comparison of results is difficult because of the poor definition of lymphedema and different classifications used within the medical literature. Table V summarizes lymphedema staging systems currently used. Another point of discrepancy is the technique used to measure limb volume. Current studies suggest that the most accurate measurement technique is optometric volumetry,39 followed by the water volumetry method. Perimeter tape measurements and volume calculations are associated with considerable bias and are not interchangeable with other methods. Moreover, in many studies, information is missing about the follow-up protocol. In analyzed publications, lymphoscintigraphy was rarely performed preoperatively, and the transport index was seldom calculated. Excisional methods. The relatively small number of MEDLINE listed publications on excisional or debulking methods has historical reasons, as these techniques were mostly published before computers existed and are not quoted in modern medical search engines. Resection operations are still undertaken, especially in severe cases of lymphedema resistant to conservative therapy. Volume reduction is achieved through mass reduction of tissue but not through improvement in lymphatic drainage. Therefore, none of these operations has the potential of becoming a curative solution. Liposuction. Lymphedema appears to be associated with excessive fatty tissue deposition, although the molecular mechanisms of this clinical phenomenon are still poorly understood. Liposuction techniques, although not curing the disease, offer a valuable symptomatic treatment supported by several well-designed studies. In selected populations of compliant patients, this treatment permits an excellent volume reduction. Lymphovenous microanastomosis and supermicroanastomosis. LVA procedures possessed the highest range of quality (score, 1-9). Some studies show no

JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS Volume -, Number -

lymphedema improvement in the long term.12,18,20 In general, publications on supermicro-LVAs show a better study design than micro-LVA studies, but results are inconsistent. Therefore, there presently is no clear evidence supporting micro- and supermicro-LVAs, but also no strong evidence against it. Lympholymphatic microanastomosis. Publications on lympholymphatic anastomosis, with or without venous interpositions, have a good level of study design according to our score. However, the literature on lympholymphatic anastomosis suggests mild postoperative improvement of less than 30% volume reduction.23 Autologous lymph node transplantation. Procedures based on lymph node transplantation showed a relatively low average quality score. Our quality score was developed to preferentially assess levels of evidence for procedures in humans. Many publications in this field derive from animal studies; therefore, patient-related quality assessment criteria could not be scored. This implied a certain degree of arbitrariness but had nevertheless the advantage of transparency in the medical applicability of our score. Reduced level of evidence concerning these procedures is therefore mostly due to the paucity of human studies. From the physiologic viewpoint, transplantation of vital lymph nodes to lymphedematous regions could be beneficial. According to the Frank-Starling equation, the peripheral capillary fluid quantity produced by an adult individual at rest corresponds to approximately 10 L/day. However, in the thoracic duct, direct measurement of the lymph flow shows passage of 2 to 3 L/day in a healthy adult at rest. Where does the fluid disappear to? The answer lies in the lymph nodes. Lymph nodes not only are immunologic stations but also perform fluid reabsorption through lymph filtration.40 Thus lymph nodes also play a fundamental role in the pathophysiologic process of lymphedema because of their fluid reabsorption capacity, a feature that is often ignored. Because lymphedema has different causes, there probably is no universal surgical solution for this disease. This study demonstrated that different surgical solutions are not supported by quite the same quality of research, although most publications are in the low/very low level for supporting guideline recommendations according to the Grading of Recommendations Assessment, Development and Evaluation system.3 Surgeons must gain perspective to allow an understanding of potential indications for each procedure. CONCLUSIONS Surgeons dealing with lymphedema patients should not only master all operative procedures proposed for this disease but understand which patients may benefit from surgery. Unfortunately, comparative studies or metaanalyses are currently absent from the literature and should become a research priority. Surgeons should always inform lymphedema patients about conservative therapies and monitor the quality and effectiveness of their surgical

Hadamitzky et al 7

techniques. Even after effective surgery, physical therapy has a role in the postoperative management and can later ideally be discontinued. Currently, efforts are being made in providing postgraduate international training on lymphatic diseases to improve their specialized management in several countries. In this context, multicenter cooperation studies should be performed to improve surgical methods for the management of lymphedema. Surgery represents a single intervention. It can potentially spare a lifelong palliation of the symptoms with manual lymphatic drainage that has proven benefits but has the disadvantage of providing only symptomatic relief to severely disabled patients. When cross referencing of a research group had to be used, references were preceded by “eg.” AUTHOR CONTRIBUTIONS Conception and design: CH Analysis and interpretation: CH, RP, PM Data collection: CH Writing the article: CH Critical revision of the article: RP, KG Final approval of the article: RP, KG, PV Statistical analysis: Not applicable Obtained funding: CH, KG Overall responsibility: CH REFERENCES 1. Addiss DG, Brady MA. Morbidity management in the Global Programme to Eliminate Lymphatic Filariasis: a review of the scientific literature. Filaria J 2007;6:2. 2. Hadamitzky C, Pabst R. Acquired lymphedema: an urgent need for adequate animal models. Cancer Res 2008;68:343-5. 3. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, AlonsoCoello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. 4. Brorson H. Liposuction normalizesdin contrast to other therapiesd lymphedema-induced adipose tissue hypertrophy. Handchir Mikrochir Plast Chir 2012;44:348-54. 5. Brorson H, Ohlin K, Olsson G, Karlsson MK. Breast cancererelated chronic arm lymphedema is associated with excess adipose and muscle tissue. Lymphat Res Biol 2009;7:3-10. 6. Schaverien MV, Munro KJ, Baker PA, Munnoch DA. Liposuction for chronic lymphoedema of the upper limb: 5 years of experience. J Plast Reconstr Aesthet Surg 2012;65:935-42. 7. Boccardo F, Fulcheri E, Villa G, Molinari L, Campisi C, Dessalvi S, et al. Lymphatic microsurgery to treat lymphedema: techniques and indications for better results. Ann Plast Surg 2013;71:191-5. 8. Campisi C, Bellini C, Campisi C, Accogli S, Bonioli E, Boccardo F. Microsurgery for lymphedema: clinical research and long-term results. Microsurgery 2010;30:256-60. 9. Campisi C, Boccardo F, Zilli A, Maccio A, Napoli F. The use of vein grafts in the treatment of peripheral lymphedemas: long-term results. Microsurgery 2001;21:143-7. 10. Auba C, Marre D, Rodriguez-Losada G, Hontanilla B. Lymphaticovenular anastomoses for lymphedema treatment: 18 months postoperative outcomes. Microsurgery 2012;32:261-8. 11. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: a prospective study. Plast Reconstr Surg 2010;126:752-8. 12. Damstra RJ, Voesten HG, van Schelven WD, van der Lei B. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with

8 Hadamitzky et al

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

JOURNAL OF VASCULAR SURGERY: VENOUS AND LYMPHATIC DISORDERS --- 2014

breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 2009;113:199-206. Demirtas Y, Ozturk N, Yapici O, Topalan M. Comparison of primary and secondary lower-extremity lymphedema treated with supermicrosurgical lymphaticovenous anastomosis and lymphaticovenous implantation. J Reconstr Microsurg 2010;26:137-43. Filippetti M, Santoro E, Graziano F, Petric M, Rinaldi G. Modern therapeutic approaches to postmastectomy brachial lymphedema. Microsurgery 1994;15:604-10. Gloviczki P, Fisher J, Hollier LH, Pairolero PC, Schirger A, Wahner HW. Microsurgical lymphovenous anastomosis for treatment of lymphedema: a critical review. J Vasc Surg 1988;7:647-52. Huang GK. Ergebnisse microchirurgischer lymphvenöser Anastomosen bei Lymphödemen. Bericht über 110 Fälle. Langenbecks Arch Chir 1989;374:194-9. Koshima I, Nanba Y, Tsutsui T, Takahashi Y, Itoh S, Fujitsu M. Minimal invasive lymphaticovenular anastomosis under local anesthesia for leg lymphedema: is it effective for stage III and IV? Ann Plast Surg 2004;53:261-6. Maegawa J, Yabuki Y, Tomoeda H, Hosono M, Yasumura K. Outcomes of lymphaticovenous side-to-end anastomosis in peripheral lymphedema. J Vasc Surg 2012;55:753-60. Matsubara S, Sakuda H, Nakaema M, Kuniyoshi Y. Long-term results of microscopic lymphatic vesseleisolated vein anastomosis for secondary lymphedema of the lower extremities. Surg Today 2006;36:859-64. Vignes S, Boursier V, Priollet P, Miserey G, Trevidic P. Évaluations quantitative et qualitative des résultats de l’anastomose lymphoveineuse chirurgicale dans les lymphoedèmes des membres inférieurs. J Mal Vasc 2003;28:30-5. Yamamoto Y, Sugihara T. Microsurgical lymphaticovenous implantation for the treatment of chronic lymphedema. Plast Reconstr Surg 1998;101:157-61. Springer S, Koller M, Baumeister RG, Frick A. Changes in quality of life of patients with lymphedema after lymphatic vessel transplantation. Lymphology 2011;44:65-71. Weiss M, Baumeister RG, Hahn K. Post-therapeutic lymphedema: scintigraphy before and after autologous lymph vessel transplantation: 8 years of long-term follow-up. Clin Nucl Med 2002;27: 788-92. Belcaro G, Errichi BM, Cesarone MR, Ippolito E, Dugall M, Ledda A, et al. Lymphatic tissue transplant in lymphedemada minimally invasive, outpatient, surgical method: a 10-year follow-up pilot study. Angiology 2008;59:77-83. Tobbia D, Semple J, Baker A, Dumont D, Johnston M. Experimental assessment of autologous lymph node transplantation as treatment of postsurgical lymphedema. Plast Reconstr Surg 2009;124:777-86. Hadamitzky C, Blum KS, Pabst R. Regeneration of autotransplanted avascular lymph nodes in the rat is improved by platelet-rich plasma. J Vasc Res 2009;46:389-96.

27. Becker C, Arrive L, Saaristo A, Germain M, Fanzio P, Batista BN, et al. Surgical treatment of congenital lymphedema. Clin Plast Surg 2012;39: 377-84. 28. Becker C, Assouad J, Riquet M, Hidden G. Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation. Ann Surg 2006;243:313-5. 29. Cheng MH, Chen SC, Henry SL, Tan BK, Lin MC, Huang JJ. Vascularized groin lymph node flap transfer for postmastectomy upper limb lymphedema: flap anatomy, recipient sites, and outcomes. Plast Reconstr Surg 2011;131:1286-98. 30. Gharb BB, Rampazzo A, Spanio di Spilimbergo S, Xu ES, Chung KP, Chen HC. Vascularized lymph node transfer based on the hilar perforators improves the outcome in upper limb lymphedema. Ann Plast Surg 2011;67:589-93. 31. Lin CH, Ali R, Chen SC, Wallace C, Chang YC, Chen HC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg 2009;123:1265-75. 32. Saaristo AM, Niemi TS, Viitanen TP, Tervala TV, Hartiala P, Suominen EA. Microvascular breast reconstruction and lymph node transfer for postmastectomy lymphedema patients. Ann Surg 2012;255:468-73. 33. Slavin SA, Van den Abbeele AD, Losken A, Swartz MA, Jain RK. Return of lymphatic function after flap transfer for acute lymphedema. Ann Surg 1999;229:421-7. 34. Viitanen TP, Maki MT, Seppanen MP, Suominen EA, Saaristo AM. Donor-site lymphatic function after microvascular lymph node transfer. Plast Reconstr Surg 2012;130:1246-53. 35. Mehrara BJ, Zampell JC, Suami H, Chang DW. Surgical management of lymphedema: past, present, and future. Lymphat Res Biol 2011;9: 159-67. 36. Warren AG, Brorson H, Borud LJ, Slavin SA. Lymphedema: a comprehensive review. Ann Plast Surg 2007;59:464-72. 37. Cormier JN, Rourke L, Crosby M, Chang D, Armer J. The surgical treatment of lymphedema: a systematic review of the contemporary literature (2004-2010). Ann Surg Oncol 2012;19:642-51. 38. Hoffmann JN, Fertmann JP, Baumeister RG, Putz R, Frick A. Tumescent and dry liposuction of lower extremities: differences in lymph vessel injury. Plast Reconstr Surg 2004;113:718-24; discussion: 725-6. 39. Lee MJ, Boland RA, Czerniec S, Kilbreath SL. Reliability and concurrent validity of the perometer for measuring hand volume in women with and without lymphedema. Lymphat Res Biol 2011;9:13-8. 40. Levick JR. Capillary filtration-absorption balance reconsidered in light of dynamic extravascular factors. Exp Physiol 1991;76:825-57.

Submitted Jun 1, 2013; accepted Feb 9, 2014.