Axillary vein abnormalities contribute to development of lymphedema after surgery for breast cancer.

Axillary vein abnormalities contribute to development of lymphoedema after surgery for breast cancer.

Br J Surg. 2005 Mar

Pain SJ, Vowler S, Purushotham AD.
Cambridge Breast Unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.

email: A. D. Purushotham (amy.byrtus@addenbrookes.nhs.uk)

*Correspondence to A. D. Purushotham, Cambridge Breast Unit, Box 97, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UKPresented in part to a meeting of the Association of Surgeons of Great Britain and Ireland, Manchester, UK, May 2003, and to the Nottingham International Breast Meeting, Nottingham, UK, September 2003

Conference: Association of Surgeons of Great Britain and Ireland, Manchester, UK, May 2003

Conference: Nottingham International Breast Meeting, Nottingham, UK, September 2003
Funded by: Addenbrooke's Charities

BACKGROUND: The aetiology of breast cancer-related lymphoedema (BCRL) is poorly understood and multifactorial. Previous work has suggested that acquired abnormalities of the axillary vein may contribute to arm swelling. This prospective study evaluated venous changes in patients with a new diagnosis of breast cancer who had surgery that included axillary lymph node clearance.

METHODS: Patients underwent arm volume measurement and Doppler ultrasonographic assessment of the axillary vein before, and at 3 and 12 months after surgery.

RESULTS: A complete data set was available for 70 patients. BCRL was observed in 16 per cent at 3 months and 11 per cent at 12 months. Significant alterations to venous flow patterns were observed in those with BCRL. Vein wall movement was significantly reduced after surgery for the group as a whole, but did not correlate with arm swelling. Venous stenosis with impaired flow was also observed in the absence of BCRL.

CONCLUSION: Axillary clearance can cause altered flow within the axillary vein, which is associated with an increased risk of developing lymphoedema. Copyright (c) 2005 British Journal of Surgery Society Ltd.

Wiley InterScience

Short-term effects of axillary lymph node clearance surgery on lymphatic physiology of the arm in breast cancer.

J Appl Physiol. 2005 Dec

Pain SJ, Barber RW, Solanki CK, Ballinger JR, Britton TB, Mortimer PS, Purushotham AD, Peters AM.

Cambridge Breast Unit, Addenbrooke's Hospital, UK.

It is not known why some women develop breast cancer-related lymphedema (BCRL) of the arm, whereas others having similar treatment do not. We speculated that increased uptake of protein into local blood may protect against BCRL. Sixteen women were given bilateral subcutaneous hand webspace injections of polyclonal immunoglobulin (HIgG), (99m)Tc-HIgG on one side and (111)In-HIgG on the other, before and 3 mo after axillary clearance surgery.

The rates of clearance of activity from the depot (k) and accumulation in central blood (b(contra)) were measured using a scintillation probe and bilateral antecubital vein blood sampling, respectively.

Activity accumulating in blood ipsilateral to the injected side, in excess of central blood activity (b(ipsi)) was also calculated as a measure of local vascular uptake. The k correlated with b(contra), but neither changed in response to surgery. However, b(ipsi) for injections of (99m)Tc-HIgG into the affected arm increased in all seven patients in whom data were available (0.018 +/- 0.006 to 0.038 +/- 0.007%/min; P <>

We conclude that uptake of protein into local blood and/or proteolysis increases after axillary surgery and may protect against BCRL.

Full Text Article

Lymph Node Status and Breast Cancer-related Lymphedema

Lymph Node Status and Breast Cancer-related Lymphedema.

Purushotham AD, Britton TM, Klevesath MB, Chou P, Agbaje OF, Duffy SW.
From *King’s College London and Guy’s and St. Thomas’ NHS Foundation Trust; †Department of Surgery, Ipswich Hospital NHS Trust; and ‡Centre for Epidemiology, Mathematics and Statistics, Cancer Research, London, United Kingdom.

OBJECTIVE: This study examines the association between nodal positivity and risk of developing breast cancer-related lymphedema (BCRL) in patients who underwent axillary lymph node dissection (ALND).

SUMMARY BACKGROUND DATA: The pathophysiology of BCRL is poorly understood. It has been assumed that one of the factors predisposing to the development of BCRL is nodal positivity, although retrospective series have produced contradictory findings. As these studies have included treatment regimens known to cause BCRL, such as axillary radiotherapy, any relationship between nodal positivity and the development of BCRL remains speculative.

METHODS: A total of 212 patients who had undergone ALND for invasive breast cancer had arm volume measurements preoperatively, and at intervals postoperatively. No patient received axillary radiotherapy. Arm volumes were obtained by measuring serial arm circumferences every 4 cm up the arm and then calculated by using the formula for the volume of a truncated cone. Robust regression techniques were used to analyze the effects of node positivity, age, preoperative body mass index, and wound infection on arm volume excess.

RESULTS: In all, 64 of 212 (30%) patients were node positive. Contrary to previous assumptions, positive node status was significantly inversely associated with arm volume after adjusting for tumor size, time since operation, and allowing for correlated observations within subjects. Furthermore, the number of positive nodes also correlated inversely with arm volume.

CONCLUSION: These results are counterintuitive to the conventional understanding of the pathophysiology of BCRL. A possible explanation is that patients who develop disease in axillary lymph nodes and subsequently undergo ALND have more time and ability to develop lymphatic collaterals, which may provide adequate lymphatic drainage following surgery, thereby reducing the risk of developing BCRL.

Article

REMINDER - LIGHTHOUSE LYMPHEDEMA NETWORK - OCTOBER PATIENT PROGRAM

LIGHTHOUSE LYMPHEDEMA NETWORK INVITES YOU TO OUR: 10th ANNUAL LYMPHEDEMA EDUCATION & AWARENESS PROGRAM:

“Lymphedema: Empowerment through Knowledge"

October 5-7, 2007

Renaissance Waverly Hotel
2450 Galleria Parkway
Atlanta GA 30339

The Lighthouse Lymphedema Network is pleased to invite you to an outstanding educational and awareness conference this fall! Continuing our annual efforts to increase awareness about lymphedema, we have assembled a terrific group of speakers to provide information on a wide variety of topics for patients, family, caregivers, and professionals. We will also have a large number of our excellent vendor associates present to demonstrate current products for lymphedema care and treatment.

Whether you are newly-diagnosed with lymphedema and eager to get more information about what it is and how it can be treated, or perhaps you are interested in learning what the latest research in this field promises, attendance at our program will definitely be beneficial. [Professionals, remember LLN offers CEUs for attendance.]

Our program starts Friday afternoon, October 5, with a pre-conference tour of Sigvaris’ garment manufacturing plant here in Atlanta, and will be followed by a Kick-Off Party from 5:00-7:00 PM. Saturday and Sunday are full of plenary sessions open to everyone, with instructional sessions for both professionals and all other conference attendees.

Lighthouse Lymphedema Network Program Info

Registration and schedule

The Lymphatics and Inflammation

The primary valves in the initial lymphatics during inflammation.

"More substantiation on the involvment of lymphedema and the body's inflammatory response system."

Lymphat Res Biol. 2007

Lynch PM, Delano FA, Schmid-Schönbein GW. Department of Bioengineering, University of California San Diego, La Jolla, California 92093-0412, USA. g...@bioeng.ucsd.edu

BACKGROUND: The primary valve system in the initial lymphatics prevents fluid transport from the initial lymphatics back into the interstitium. The authors hypothesize that since the primary valves are made up of an extraordinarily thin endothelium, they are readily compromised by mechanical or biochemical inflammatory stimuli. Thus, the opening dimension of the primary valves and their ability to prevent reflux into the interstitium during inflammation were investigated.

METHODS AND RESULTS: Acute inflammation was generated in the intact rat spinotrapezius muscle by suffusion of f-Met-Leu-Phe and platelet-activating factor. Once inflamed, the effective opening dimensions of the primary valves and the transport back out of the initial lymphatics were determined by examining the transport of fluorescent tracers from the interstitium to the lymphatics. Quantum dots and fluorescently labeled albumin readily enter initial lymphatics from the interstitium. The maximum diameter of microspheres that enter the initial lymphatics is between 0.5 microm and 0.8 microm in both control and inflamed tissue. While under control conditions no quantum dots escaped from initial lymphatics back into the interstitium, during inflammation there was extensive escape of quantum dots.

CONCLUSIONS: These results suggest that, in acute inflammation, the function of the endothelial barriers in the initial lymphatics may be compromised. A failure of the primary lymphatic valves has two consequences. First, fluid clearance from the tissue is less efficient, which causes the level of edema to increase. Second, the leaking initial lymphatics allow inflammatory mediators to accumulate in the tissue, therefore enhancing interstitial and lymphatic inflammatory reactions.

Article

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Inflammation, lymphatic function, and dendritic cell migration.

Lymphat Res Biol. 2006

Angeli V, Randolph GJ. Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York, USA. micva@nus.edu.sg

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

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Inflammatory manifestations of experimental lymphatic insufficiency.

PLoS Med. 2006 Jul

Tabibiazar R, Cheung L, Han J, Swanson J, Beilhack A, An A, Dadras SS, Rockson N, Joshi S, Wagner R, Rockson SG. Stanford Center for Lymphatic and Venous Disorders, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America.

BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic.

METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response.

CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

Article

The Dragon Boat Ladies and Lymphedema

Awaken the dragon at Portage

Lakes Friday, June 8, 2007

A Dragon Boat is coming to the Portage Lakes Saturday. The traditional Dragon Dance will be performed during the "Awakening The Dragon Ceremony" at 1:30 p.m. Saturday in Craftsmen Park at 4450 Rex Lake Dr. The new Dragon Dream Team is sponsored by Dr. Douglas Wagner.


The group will include paddlers and nonpaddling members who are breast cancer survivors. No other qualification is needed. Dragon Boat teams were launched in 1996 by Dr. Don McKenzie, a sports medicine physician at the University of British Columbia.

His team, Abreast In A Boat, tested the myth that repetitive upper-body exercise in women treated for breast cancer encourages lymphedema. "Dr. McKenzie believed that by following a special exercise and training program, women could avoid lymphedema and enjoy active, full lives," explains the Web site A Breast In A Boat "

As we followed his program, we were carefully monitored by a sports medicine physician, a physiotherapist and a nurse. Dr. McKenzie's theory was proven correct. No new cases of lymphedema occurred and none of the existing cases became worse." The Dragon Boat being launched Saturday at Portage Lakes is a 20-paddler boat (10 sit side-by-side at port and starboard, who use a canoe- type paddle. They follow the commands of a coach who sits in the back. Dragon Boat teams now are located throughout the world, and hold national and international competitions. For information, visit Dragon Dream Team.com


At Portage Lakes, the Dragon Boat team will share facilities with Portage Lakes Rowing Association. NATURE CENTER

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Area Paddlers Honour Breast Cancer Pioneer Adam Peck

Guelph June 12, 2007

A local group of breast cancer survivors is joining the University of Guelph in honouring sports medicine doctor Dr. Don McKenzie. The BreastStrokes Dragon Boat Team feels that it's McKenzie's work that has empowered them and given them hope in dealing with breast cancer. "After you have breast cancer you tend to feel quite isolated," said Marlene Jofriet, a team member. "He actually did us a great service. We call it a floating support group because you have the camaraderie and the social aspect of it," she said. The BreastStrokes team is completely made up of breast cancer survivors.

Formed in 1998, the team has 30 members of all ages and competes each summer in dragon boat festivals around the province. Following Tuesday's convocation ceremony, where McKenzie will receive an honourary doctorate, he will be presented with Jofriet's painting "Beginnings," commemorating his pioneering work for breast cancer survivors. Jofriet said dragon boating empowered her and other survivors to take action in their recovery. "After you have that, you're not quite sure what you can do.

You can either sit there and mope or be active. I choose to be active," she said. Enter McKenzie and his work. Prior to 1996, doctors told breast cancer patients to avoid strenuous activity and exercise, because it could lead to lymphedema - swelling under the arms where lymphnodes have been removed. Going against the medical science of the day, McKenzie theorized that intense exercise would not cause lymphedema and formed a dragon boat team in 1996 to test his theory.

After the summer's paddling season, the most evident effects the team felt were stronger arms and improved mental health. From those ripples, hundreds of survivor teams now flood dragon boat festivals around the world. Jofriet's painting symbolizes the struggle of breast cancer.

The dark water represents the unknown, the blue sky represents hope and the yellow dragon represents the life line. Jofriet, who has been a team member since 2001, says the team always paddles to win. "I believe in pushing the limits. So that, I do."