This past year, we had quite a discussion on a newer type of experimental treatment for lymphedema, so I have included two pages of related information,
In truth, the concept is not new and I found an article first published in 1981 proposes lymph vessel transplantation and subsequently an experiment on dogs.
Obviously, after the passage of twenty six years, if this method were successful, we would have heard more about it and more research information would have been published.
It is my personal opinion, that in the long term, these two methods might well prove more dangerous than beneficial and I would be opposed to their use.
First, one of the biting questions of lymphedema research is “why is it that 60% of breast cancer patients do NOT get lymphedema?”
Research in that area proposes that perhaps those that DO get lymphedema already have a compromised or “at risk” lymph system.
Thus by removing lymph vessels or nodes from one area to reimplant in another simply makes a trade on the location of the at risk area, so what actually is gained or what is the benefit for the patient?
One study following transplant was done eight years after the surgical procedure. However, it is important to realize that lymphedema does not automatically appear immediately after the removal or destruction of either lymphatic vessels, tissue or nodes.
Many times it doesn’t appear for ten or more years. So clearly, more research and study needs to be done on these two techniques. Once it does occur, however, it is at this time a life long condition with no cure..
One more consideration is that the nodes to be transplanted are removed from the inguinal area. Radiological studies have clearly proved that my hereditary lymphedema is caused by the lack of development of numerous nodes in that exact area, both on the right and left sides of my body.
To remove nodes in this critical region is to put the patient at high risk for subsequent development of leg lymphedema. If you trade arm lymphedema for leg lymphedema, have you really helped the patient?
In the meantime, I simply can not recommend it.
Be safe – be well.
* Becker C, * Assouad J, * Riquet M, * Hidden G.
Service de Chirurgie Thoracique, Hopital Europeen Georges Pompidou, Paris, France.
BACKGROUND AND OBJECTIVES: Lymphedema complicating breast cancer treatment remains a challenging problem. The purpose of this study was to analyze the long-term results following microsurgical lymph node (LN) transplantation.
METHODS Twenty-four female patients with lymphedema for more than 5 years underwent LN transplantation. They were treated by physiotherapy and resistant to it. LNs were harvested in the femoral region, transferred to the axillary region, and transplanted by microsurgical procedures. Long-term results were evaluated according to skin elasticity, decrease, or disappearance of lymphedema assessed by measurements, isotopic lymphangiography, and ability to stop physiotherapy.
RESULTS The postoperative period was uneventful; skin infectious diseases disappeared in all patients. Upper limb perimeter returned to normal in 10 cases, decreased in 12 cases, and remained unchanged in 2 cases. Five of 16 (31%) isotopic lymphoscintigraphies demonstrated activity of the transplanted nodes. Physiotherapy was discontinued in 15 patients (62.5%). Ten patients were considered as cured, important improvement was noted in 12 patients, and only 2 patients were not improved.
CONCLUSION LN transplantation is a safe procedure permitting good long-term results, disappearance, or a noteworthy improvement, in postmastectomy lymphedema, especially in the early stages of the disease.
Case Lymphedema complicating breast cancer treatment remains a challenging problem. Combined physiotherapy is not performed equally in all centers, and many physicians remain skeptical on the overall efficacy of surgical treatments.1 Furthermore, whatever the treatment proposed, the possibility of cure remains questionable. Over the last 12 years, our team has treated limb lymphedema by transplanting lymph nodes.2 The purpose of this study was to analyze the results obtained with this procedure during a minimal 5-year follow-up.
Patients and Methods We retrospectively reviewed data of 24 female patients suffering from lymphedema following breast cancer treatment who underwent lymph node transplantation by one of us (C.B.) in Cavell Institution in Brussels from 1991 to 1997. Mean age was 58.7 years (range, 37–80 years) with a mean follow-up of 8.3 years (range, 5–11 years). Upper limb lymphedema was right sided in 14 patients and left sided in 10 patients. All the patients were previously seen by their oncologist and considered in breast cancer remission. Breast carcinoma treatment performed was mastectomy (n = 3), mastectomy and radiation therapy (n = 11), and mastectomy, radiation therapy, and chemotherapy (n = 10). Axillary lymphadenectomy had been performed in all cases. In 18 patients, upper limb lymphedema was present for at least 1 year or greater (mean, 5.6 years; range, 1–15 years). In 6 patients, it was present for only a few months (mean, 5 months; range, 3–8 months). Patients complaining of pain and/or presenting with palsy and/or with elephantiasis were excluded from the study. All patients were undergoing physiotherapy and were considered resistant to it.
Lymphedema was assessed by measurements, infectious episodes, and isotopic lymphangiography.
Measurements were weekly during the preoperative month and were performed before and after physiother-apy. Sites measured were at the wrist, 10 cm above the wrist, at the elbow, and 10 cm above the elbow. Results were then compared with the contralateral limb measurements.
The number of previous infectious episodes (erysipela, lymphangitis…) and the aspect of the teguments at presentation (elasticity of the skin and infectious disease) were recorded. In case of infectious disease, antibiotic therapy and local treatment was performed.
Isotopic lymphangiography was performed in 20 patients. In 15 patients, lymphoscintigraphy demonstrated absence of both lymph nodes and drainage; and in 3 patients, drainage was impaired without clearly demonstrating the absence of nodes. In 2 patients, lymphoscintigraphy was normal.
Patients were divided into 2 stages: stage I, early edema with no or less than 2 infectious episodes, skin elasticity preserved, and perimeter not exceeding 30% more than the contralateral arm (n = 6); stage II, older edema, most often of more than 1 year duration, more than 2 infectious episodes, impaired skin elasticity, and perimeter measured between 30 and 50% more than the contralateral arm (n = 18).
Surgical approach of the axillary region of the lymph-edematous limb was performed in search of receiving vessels: fibrotic muscular and burned tissue were dissected and ad-hesions released. Axillary vessels were dissected and the periscapular pedicle was isolated. The circumflex posterior branches were individualized and prepared for microanas-tomoses.
An incision was then performed in the inguinal region. The dissection began by visualizing the superficialis circumflex iliac vein. At that level are located lymph nodes irrigated by the circumflex iliac vessels and without direct connection with the lymphatic drainage of the inferior limb. These nodes were dissected, freed, and elevated external to internal at the level of the muscular aponeurosis. The nodes were then harvested with an abundant amount of surrounding fat tissue.
Lymph nodes were then transplanted in the axillary receiving site. Artery and vein were anastomosed with the vessels previously prepared, using microsurgical techniques. Both axillary and inguinal approaches were closed on suction drainage.
In 7 cases, because of an incomplete result at the level of the forearm, a second procedure was performed. Lymph nodes were harvested in the same manner at the contralateral inguinal site and were transplanted at the level of the elbow.
Following surgery, manual drainage (physiotherapy) was performed on the first postoperative day and daily during the first 3 months. Manual drainage was then performed twice a week during the following 3 months and discontinued. No elastic compression dressing was applied following surgery to avoid compression on the transplanted lymph nodes and on the microsurgical anastomosis. Antisludge treatment mainly acetylsalicylates were administrated during the postoperative period.
Long-term results were evaluated according to skin elasticity and existence of infectious disease, decrease or disappearance of the lymphedema assessed by measurements, effects observed on isotopic lymphangiography, and ability to stop or to discontinue physiotherapy after 6 months. Long-term results were also evaluated according to the duration of the lymphedema before surgery and occurrence of downstaging after surgery.
Results The postoperative period was uneventful except for the appearance of lymphorrhea in 8 patients, which resolved over a few days. Infectious disease disappeared totally in 17 patients; and in the remaining 7 patients, only one episode of skin infectious disease was recorded.
Upper limb perimeter returned to normal in 10 cases, remained unchanged in 2 cases, and decreased more than 50% of its value in 6 patients and less than 50% of its value in 6 other patients.
Control isotopic lymphangiography was performed in 16 patients. In 11 patients, lymph nodes and lymph drainage were initially absent: in 4 patients, the transplanted lymph nodes were visualized and new lymph drainage pathways appeared. In 3 patients, lymph drainage was impaired without clearly demonstrating lymph nodes: in 1 of these patients, lymph node was visualized. In 2 patients with normal isotopic lymphangiography, results were unchanged. So, 5 of 16 (31%) lymphoscintigraphies demonstrated the effectiveness of lymph node transplantation.
Physiotherapy was discontinued after 6 months in 14 patients and after 12 months in 1 patient. In the 9 other patients, physiotherapy remained necessary and was performed once weekly in 7 patients. Physiotherapy was thus discontinued in 15 patients (62.5%).
Ten patients were considered cured (good results) (stage I, n = 4; stage II, n = 6). Two patients were not at all improved, lymphedema remaining unchanged (stage I, n = 1; stage II, n = 1). Downstaging (from stage II to stage I) was observed in 12 patients.
Duration of the lymphedema before surgery was: a few months (n = 5) and 1 to 4 years, mean 2.4 years (n = 5) in case of good results, 3 and 4 years in case of bad results (n = 2), 8 months and 1 to 15 years, mean 7.4 years (n = 11) in case of downstaging. In 1 patient with downstaging, the result was considered as good (normalized) following elective liposuction.
During long-term follow-up, no breast cancer recurrence was observed.
Discussion Autologous lymph node transplantation permits lymph-edema improvement with long-term downstaging commonly obtained (except 2 patients), and physiotherapy discontinued in 62.3% of patients. Lymphedema was considered cured in 42% of patients and fixating lymph nodes were detected in 31% of patients controlled by lymphoscintigraphy. Good results were obtained more regularly when the duration of lymphedema was the shortest before lymph nodes transplantation. Effectiveness of the procedure was always durably demonstrated with respect to skin infectious diseases.
Autologous lymph node transplantation for lymphedema treatment is a recent microsurgical technique,3 the results of which have yet to be fully evaluated.4 Results of the transplantation of lymph nodes in the rat5,6 and in the dog7 prove very attractive. In humans, the major concern is to find a fatty flap containing lymph nodes with their own vascularization, the procurement of which should be performed without injury. Our technique uses inguinal lymph node free flap2 made of the more superior external superficial lymph nodes: an anatomic study based on the dissection of 50 inguinal regions of fresh cadavers demonstrated that they mainly received lymph from the abdominal wall and that their procurement did not impair lymph drainage of the lower limb.6 This procurement site is the only one used in this report; however, lymph node transplantation may be used to treat limb lymphedema with other procurement sites such as cervical2 or axillary8 being possible.
No current gold standard for evaluation of lymphedema exists;9 hence, evaluating results of treatments remains difficult and appears controversial. Fluid displacement data, which would have been a more objective methodology, was not available because it was not routinely performed. Despite this, and although circumferential data appear subjective and difficult to interpret, results on lymphedema measurements were satisfactory in this series, and many patients were able to discontinue physiotherapy treatments.
Trevidic and Pecking9 have underlined the role lymphoscintigraphy may have to objectively assess results obtained and to select patients for surgery. However, in our series, results obtained on reappearance of lymph drainage are difficult to interpret meaningfully, and colloidal uptake by transplanted lymph nodes was detected in only 31% of patients. Appearance of lymphatic pathways toward the graft site, which was sometimes also present, could suggest a “lymphangiogenetic” effect of these grafts. These results, also observed in experimental studies,5–7 would be of paramount interest if confirmed by other series.
Transplanted lymph node colloidal uptake was all the more frequent than the duration of lymphedema was shorter. Shesol et al5 also observed, in a study in the rat, that ra-dioactivity appeared in 4 of 5 transplanted lymph nodes when transplantation was immediately following lymphedema onset, whereas it appeared in only 1 of 5 cases when transplantation was delayed. This could suggest that it would be perhaps better not to delay the indication for lymph node transplantation.
Effect on skin infectious diseases was the most obvious. A role by the transplanted lymph nodes immune effect may be possible. Experimental studies have demonstrated that autotransplanted lymph nodes rapidly recovered a normal architecture.10 No study is available to validate our observations, but Egawa et al11 reported reduction of lymphedema after intraarterial injection of autologous lymphocytes probably due to changes in blood protein components. Lymphoid tissue present in transplanted lymph nodes may prevent in-fection but may also reduce arm swelling by similar mechanism of changes in protein components: this also may explain partial benefits obtained when lymphatic pathways are not restored.
Conclusion Autologous lymph node transplantation appears to have a favorable and persistent effect on postmastectomy lymphedema. It is a safe procedure that may be advocated when discussing surgical treatments, especially in early stages of the disease.
Footnotes Reprints: Marc Riquet, MD, PhD, Service de Chirurgie Thoracique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75015 Paris Cedex, France. E-mail: email@example.com.
Földi M. Treatment of lymphoedema. Lymphology. 1994;27:1–5. PubMed. 2.Becker C, Hidden G, Godart S, et al. Free lymphatic transplant. Eur J Lymphol Rel Prob. 1991;6:25–77. 3.Bernars MJ, Witte CL, Witte MH, et al. The diagnosis and treatment of peripheral lymphedema: draft revision of the 1995 consensus document of the International Society of Lymphology Executive Committee for Discussion at the September 3–7, 2001 XVIII International Congress of Lymphology in Genoa, Italy. Lymphology. 2001;34:84–91. PubMed. 4.Campisi C. Surgery for the treatment of lymphedema. Eur J Lymph Rel Prob. 2002;10:24–27. 5.Shesol BF, Nakashima R, Alavi A, et al. Successful lymph node transplantation in rats, with restoration of lymphatic function. Plast Recontr Surg. 1979;63:817–823. 6.Becker C, Hidden G. Transfert de lambeaux lymphatiques libres. Microchirurgie et étude anatomique. J Mal Vascul. 1988;13:199–122. 7.Chen HC, O'Brien MC, Roger IW, et al. Lymph node transfer for the treatment of obstructive lymphoedema in the canine model. Br J Plast Surg. 1990;43:578–586. PubMed. 8.Trevidic P, Cormier JM. Free axillary lymph node transfer. In: Cluzan RV, ed. Progress in Lymphology, vol. XIII. Excerpta Medica Paris. 1992:415–420. 9.Trevidic P, Pecking AP. Limb radionuclide lymphoscintigraphy prior and after a lymphatic bypass using an axillary flap. Lymphology. 1998;31(suppl):605–608. 10.Rabson JA, Geyer SJ, Levine G, et al. Tumor immunity in rat lymph nodes following transplantation. Ann Surg. 1982;196:92–99. PubMed. 11.Egawa Y, Sato A, Katoh I, et al. Reduction in arm swelling and changes in protein components of lymphoedema fluid after intra arterial injection of autologous lymphocytes. Lymphology. 1993;26:169–176. PubMed.
PMID: 16495693 PubMed - indexed for MEDLINE
Corinne Beckera, Duc Nhat Minh Phama, Jalal Assouada, Alain Badiaa, Christophe Foucaulta and Marc Riquet, a, aService de Chirurgie Thoracique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75015 Paris Cedex, France
Received 2 October 2007; revised 13 November 2007; accepted 19 December 2007. Available online 1 May 2008.
Abstract Postmastectomy chronic pain may be divided into widespread and regional pain. Almost half patients with regional pain, which is more likely related to neuropathic phenomena, do not benefit any pain relief from medication. Our purpose was to report results on pain relief obtained by axillary lymph nodes autotransplantation.
Methods Six patients presented with chronic regional neuropathic pains and upper limb lymphedema after breast cancer surgery and radiation therapy. Despite medication, pain was intolerable and daily activity dramatically reduced. Lymph nodes were harvested in the femoral region, transferred to the axillary region and transplanted by microsurgical procedures.
Results Lymphedema resolved in 5 out of 6 patients. Pain was relieved in all, permitting return to work and daily activity; analgesic medication was discontinued.
Conclusion This procedure proved efficient and may be advocated in case of neuropathic pain when discussing lymphedema management.
Keywords: Breast cancer; Lymphedema; Chronic pain; Lymph node; Neuroma; Autotransplantation
Francois CG, Brouha PC, Laurentin-Perez LA, Perez-Abadia G, Grossi FV, Barker JH, Hewitt CW, Kon M, Ramsamooj R, Maldonado C. Plastic Surgery Research, Department of Surgery, University of Louisville, KY, USA.
BACKGROUND The role of lymph nodes (LNs) in adaptive immune responses has been the subject of extensive research. In previous studies, the surgical removal of lymph nodes from rat hind limbs prevented the development of lethal graft-versus-host disease (GVHD) after allogeneic hind limb transplantation to chimeric recipient rats. The purpose of this study was to establish the role of the cellular fraction versus the microenvironment of LNs in the development of GVHD in this model.
METHODS A rat model for vascularized LN transplantation was developed and graft-versus-host responses were compared after: 1) naive ACI LN cells were infused into Wistar-Furth (WF) rats as chimeric recipients (e.g. [ACI–>WF]); 2) vascularized WF lymph nodes were transplanted to syngeneic WF recipients; 3) nonvascularized ACI lymph nodes were transplanted to [ACI–>WF] chimeric recipients; 4) vascularized ACI lymph nodes were transplanted to [ACI–>WF] chimeric recipients.
RESULTS Transplantation of vascularized ACI lymph nodes to [ACI–>WF] chimeric recipient rats resulted in severe and sometimes lethal GVHD. In contrast, neither the infusion of purified ACI LN cells nor the transplantation of nonvascularized LNs led to GVHD in chimeric recipients.
CONCLUSIONS When introducing allogeneic cells into chimeric recipients, concomitant transplantation of the vascularized LN microenvironment makes a manifest difference between induction and absence of GVHD. This illustrates the important role of the LN microenvironment in adaptive immune responses.
An artificial lymph node has been transplanted into mice, where it successfully produced immune cells. The new form of bioengineered tissue marks a significant step towards transplanting an entire immune system into patients dying of AIDS, cancer or other diseases, say the researchers who carried out the transplant.
Takeshi Watanabe at the RIKEN Institute in Japan and colleagues used a “bioscaffold” made of collagen impregnated with stromal and dendritic cells extracted from the thymus of newborn mice. The entire package – a collagen sponge about 3 to 4 millimetres across – was then implanted into mice with healthy immune systems that had been vaccinated against a harmless antigen (something that triggers an immune response).
In a natural lymph node, stromal cells act as “organiser” cells, arranging the various components of the node and aiding its development. Watanabe found that the same was true of the artificial nodes. The implanted stromal cells attracted T and B immune cells (lymphocytes) that were already circulating in the healthy mouse, then organised them into compartments segregated from one another, just as they appear in natural nodes.
Empty nodes After the artificial node had filled with antigen-specific T and B cells, Watanabe transplanted it into a mouse with no functioning immune system. The lymphocytes quickly spread out from the artificial node into the animals' own lymph nodes, which lay empty due to the lack of immune activity.
When Watanabe injected the same harmless antigen into the immuno-deficient mouse, its transplanted immune system responded vigorously, producing massive numbers of lymphocytes to neutralise the foreign molecule. After a month, these cells’ “memory” was still maintained, and they were able to fight off challenges from the antigen.
“It’s one tiny step towards use in humans,” says Watanabe. “The next step is to use human cells in humanised mice. Then, maybe in four or five years, we might be able to make the first prototypes of a human model.”
Eventually, Watanabe hopes this technology will provide a revolutionary treatment for patients with AIDS or cancer.
By implanting artificial nodes plump with healthy T and B cells in AIDS patients, he believes he might be able to revitalise their damaged immune systems. For cancer, he hopes to adopt a similar approach in which the transplanted nodes will contain T cells trained to hunt down the antigens produced by tumour cells and kill them off.
Journal reference: Journal of Clinical Investigation, doi:10.1172/JCI30379
Plast Reconstr Surg. 2009 Sep
Tobbia D, Semple J, Baker A, Dumont D, Johnston M. Brain Sciences Program, Department of Laboratory Medicine and Pathobiology, and Molecular and Cell Biology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada.
BACKGROUND: The authors' objective was to test whether the transplantation of an autologous lymph node into a nodal excision site in sheep would restore lymphatic transport function and reduce the magnitude of postsurgical lymphedema.
METHODS: As a measure of lymph transport, iodine-125 human serum albumin was injected into prenodal vessels at 8 and 12 weeks after surgery, and plasma levels of the protein were used to calculate the transport rate of the tracer to blood (percent injected per hour). Edema was quantified from the circumferential measurement of the hind limbs.
RESULTS: The transplantation of avascular lymph nodes at 8 (n = 6) and 12 weeks (n = 6) produced lymphatic function levels of 12.3 +/- 0.5 and 12.6 +/- 0.8, respectively. These values were significantly less (p < 0.001) than those measured at similar times in the animals receiving sham surgical procedures (16.6 +/- 0.7, n = 6; and 16.1 +/- 0.7, n = 6, respectively). When vascularized transplants were performed, lymphatic function was similar to the sham controls and significantly greater (p < 0.001) than that of the avascular group (8 weeks, 15.8 +/- 0.9, n = 8; 12 weeks, 15.7 +/- 1.0, n = 10). Lymph transport correlated significantly with the health of the transplanted nodes (scaled with histologic analysis) (p < 0.0001). The vascularized node transplants (n = 18) were associated with the greatest clinical improvement, with the magnitude of edema in these limbs exhibiting significantly lower levels of edema (p = 0.039) than nontreated limbs (n = 18).
CONCLUSIONS: The successful reimplantation of a lymph node into a nodal excision site has the potential to restore lymphatic function and facilitate edema resolution. This result has important conceptual implications in the treatment of postsurgical lymphedema.
Cheng MH, Huang JJ, Nguyen DH, Saint-Cyr M, Zenn MR, Tan BK, Lee CL.
Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
OBJECTIVE: Vascularized groin lymph node flaps have been successfully transferred to the wrist to treat postmastecomy upper limb lymphedema. This study investigated the anatomy, mechanism and outcome of a novel vascularized submental lymph node (VSLN) flap transfer for the treatment of lower limb lymphedema.
METHODS: Bilateral regional submental flaps were dissected from three fresh adult cadavers for histological study. A unilateral submental flap was dissected in another six fresh cadavers after latex injection. The VSLN flap was transferred to the ankles of seven lower extremities in six patients with chronic lower extremity lymphedema.. The mean patient age was 61±1.4years. The average duration of lymphedema symptoms was 71±42.2months.
RESULTS: There was a mean of 3.3±1.5 lymph nodes around the submental artery typically at the junction with the facial artery, on the six cadaveric histological sections. Mean of 2.3±0.8 sizable lymph nodes were dissected and supplied by the submental artery in six cadaveric latex-injected submental flaps. All seven VSLN flaps survived. One flap required re-exploration for venous congestion but was successfully salvaged. There was no donor site morbidity. At a mean follow-up of 8.7±4.2months, the mean reduction of the leg circumference was 64±11.5% above the knee, 63.7±34.3% below the knee and 67.3±19.2% above the ankle.
CONCLUSION: The transfer of a vascularized submental lymph node flap to the ankle is a novel approach for the effective treatment of lower limb lymphedema.
Clearly, while this procedure has been somewhat helpful in the short term, we still do not have enough information to say definitvely that removal of nodes from one area to transplant to another does NOT make the donor site an at risk area. We still need long term follow-up and research.
Pat Sept. 11, 2009
Vascularized Lymph Node Transfer Based on the Hilar Perforators Improves the Outcome in Upper Limb Lymphedema. PubMed
Growth factor therapy and autologous lymph node transfer in lymphedema. PubMed
Effects of autotransplanted lymph node fragments on the lymphatic system in the pig model. Feb 2010
Keywords: Lymph node transplantation - Lymphedema - Dermal backflow - SPECT/CT
Alternatives to Standard Treatment of Lymphedema–Other Un-Proven Modalities