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Axillary reverse mapping: Five-year experience

      Background

      We hypothesize that mapping the lymphatic drainage of the arm with blue dye (axillary reverse mapping [ARM]) during axillary lymphadenectomy decreases the likelihood of disruption of lymphatics and subsequent lymphedema.

      Methods

      This institutional review board-approved study involved 360 patients undergoing sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) from May 2006 to October 2011. Technetium sulfur colloid (4 mL) was injected subareolarly, and 5 mL of blue dye was injected subcutaneously in the volar surface ipsilateral upper extremity (ARM). Data were collected on variations in lymphatic drainage, successful identification and protection of arm lymphatics, crossover, and occurrence of lymphedema.

      Results

      A group of 360 patients underwent SLNB and/or ALND, 348 of whom underwent a SLNB. Of those, 237 (68.1%) had a SLNB only, and 111 (31.9%) went on to an ALND owing to a positive axilla. An additional 12 of 360 (3.3%) axilla had ALND owing to a clinically positive axilla/preoperative core needle biopsy. In 96% of patients with SLNB (334/348), breast SLNs were hot but not blue; crossover (SLN hot and blue) was seen in 14 of 348 patients (4%). Blue lymphatics were identified in 80 of 237 SLN incisions (33.7%) and in 93 of 123 ALND (75.4%). Average follow-up was 12 months (range, 3–48) and resulted in a SLNB lymphedema rate of 1.7% (4/237) and ALND of 2.4% (3/123).

      Conclusion

      ARM identified substantial lymphatic variations draining the upper extremities and facilitated preservation. Metastases in ARM-identified lymph nodes were acceptably low, indicating that ARM is safe. ARM added to present-day ALND and SLNB may be useful to lesser rates of lymphedema.
      Lymphedema remains the most published complication of axillary lymph node dissection (ALND).
      • Ivens D.
      • Hoe A.L.
      • Podd T.J.
      • Hamilton C.R.
      • Taylor I.
      • Royle G.T.
      Assessment of morbidity from complete axillary dissection.
      • Somers R.G.
      • Jablon L.K.
      • Kaplan M.J.
      • Sandler G.L.
      • Rosenblatt N.K.
      The use of closed suction drainage after lumpectomy and axillary node dissection for breast cancer. A prospective randomized trial.
      • Passik S.D.
      • McDonald M.V.
      Psychosocial aspects of upper extremity lymphedema in women treated for breast carcinoma.
      • Tobin M.B.
      • Lacey H.J.
      • Meyer L.
      • Mortimer P.S.
      The psychosocial morbidity of breast cancer-related arm swelling. Psychological morbidity of lymphedema.
      • McMasters K.M.
      • Giuliano A.E.
      • Ross M.I.
      • Reintgen D.S.
      • Hunt K.K.
      • Byrd D.R.
      • et al.
      Sentinel-lymph-node biopsy for breast cancer–not yet the standard of care.
      • Leidenius M.
      • Leppanen E.
      • Krogerus L.
      • et al.
      Motion restriction and axillary web syndrome after sentinel node biopsy and axillary clearance in breast cancer.
      • Burak W.E.
      • Hollenbeck S.T.
      • Zervos E.E.
      • et al.
      Sentinel lymph node biopsy results in less post operative morbidity compared with axillary lymph node dissection for breast cancer.
      • Swenson K.K.
      • Nissen M.J.
      • Ceronsky C.
      • et al.
      Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer.
      • Rubio I.T.
      • Korourian S.
      • Cowan C.
      • Krag D.N.
      • Colvert M.
      • Klimberg V.S.
      Sentinel lymph node biopsy for staging breast cancer.
      • Kissin M.W.
      • della Rovere Q.G.
      • Easton D.
      • Westbury G.
      Risk of lymphedema following the treatment of breast cancer.
      • Delouche G.
      • Bachelot F.
      • Premont M.
      • Kurtz J.M.
      Conservation treatment of early breast cancer: long term results and complications.
      • Larson D.
      • Weinstein M.
      • Goldberg I.
      • et al.
      Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy.
      • Petrek J.A.
      • Senie R.T.
      • Peters M.
      • et al.
      Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.
      • Velanovich V.
      • Szymanski W.
      Quality of life of breast cancer patients with lymphedema.
      • Kwan W.
      • Jackson J.
      • Weir L.M.
      • et al.
      Chronic arm morbidity after curative breast cancer treatment: prevalence and impact on quality of life.
      • Silberman A.W.
      • McVay C.
      • Cohen J.S.
      • et al.
      Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique: implications for patients with breast cancer.
      • Haid A.
      • Köberle-Wührer R.
      • Knauer M.
      • et al.
      Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation.
      • Wilke L.G.
      • McCall L.M.
      • Posther K.E.
      • Whitworth P.W.
      • Reintgen D.S.
      • Leitch A.M.
      • et al.
      Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial.
      • Schrenk P.
      • Rieger R.
      • Shamiyeh A.
      • et al.
      Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.
      • Blanchard D.K.
      • Donohue J.H.
      • Reynolds C.
      • et al.
      Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer.
      • Schijven M.P.
      • Vingerhoets A.J.
      • Rutten H.J.
      • et al.
      Comparison of morbidity between axillary lymph node dissection and sentinel node biopsy.
      • Ronka R.
      • von Smitten K.
      • Tasmuth T.
      • et al.
      One-year morbidity after sentinel node biopsy and breast surgery.
      • Leidenius M.
      • Leivonen M.
      • Vironen J.
      • von Smitten K.
      The consequences of long-time arm morbidity in node-negative breast cancer patients with sentinel node biopsy or axillary clearance.
      The technique of ALND is an anatomic dissection and has changed little over the decades.
      • Klimberg S.
      • Townsend C.
      • Evers M.
      Axillary reverse mapping. Atlas of breast surgical techniques.
      The procedure itself, however, does not take into account the anatomic drainage from the breast versus that of the arm, because drainage from the arm into the axilla has only recently been published by our group.
      • Mansel R.
      • Fallowfield L.
      • Kissin M.
      • et al.
      Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.
      • Tengrup I.
      • Tennvall-Nittby L.
      • Christiansson I.
      • et al.
      Arm morbidity after breast-conserving therapy for breast cancer.
      • Werner R.S.
      • McCormick B.
      • Petrek J.A.
      • et al.
      Arm edema in conservatively managed breast cancer: obesity is a major predictive factor.
      • Harlow S.P.
      • Krag D.N.
      sentinel lymph node – why study it: implications of the B-32 Study.
      Yet, lymphedema likely results from transection of lymph vessels from the arm coursing through the axilla and is among the most distressing complications resulting from ALND.

      National Cancer Institute. Surveillance, Epidemiology and End Results Program. Available from: http://seer.cancer.gov/faststats/sites.php?site=Breast%20Cancer&stat=Incidence.

      • Sakorafas G.H.
      • Peros G.
      • Cataliotti L.
      • et al.
      Lymphedema following axillary lymph node dissection for breast cancer.
      The morbidity of lymphedema especially from an ALND is such that some surgeons have advocated sentinel lymph node biopsy (SLNB) as the only treatment for patients with 1–2 positive nodes when undergoing breast conservation surgery, with whole breast radiation (XRT), because the local regional recurrence (LRR) and overall survival (OS) are unchanged in the group with complete ALND over SLNB. There are no similar data for partial breast irradiation or mastectomy patients.
      • Giuliano A.E.
      • Hunt K.K.
      • Ballman K.V.
      • Beitsch P.D.
      • Whitworth P.W.
      • Blumencranz P.W.
      • et al.
      Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.
      Indeed, this treatment approach has only limited experience and follow-up. Its application is also limited to specific subgroups of patients, namely, those with small, hormone-sensitive neoplasms who are clinically node negative undergoing breast conservation surgery with whole breast XRT, excluding patients who undergo partial breast XRT or mastectomy. We propose alternatively that trying to identify and spare the lymphatics draining the upper extremities may be a better approach to decreasing the morbidity from lymphadenectomy.
      • Burnett A.F.
      • Stone P.J.
      • Klimberg S.V.
      • Gregory J.L.
      • Roman J.R.
      Lower extremity glandography (LEG): a new concept to identify and enhance lymphatic preservation.
      • Boneti C.
      • Korourian S.
      • Diaz Z.
      • Santiago C.
      • Mumford S.
      • Adkins L.
      • et al.
      Scientific Impact Award: axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy.
      • Thompson M.
      • Korourian S.
      • Henry-Tillman R.
      • Adkins L.
      • Mumford S.
      • Westbrook K.C.
      • et al.
      Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation.
      We hypothesized that mapping the lymphatic drainage of the arm with blue dye (axillary reverse mapping [ARM]) to delineate and preserve the lymphatics draining the arm during lymphadenectomy added to intraoperative administration of technetium to map the drainage of the breast may decrease the likelihood of disruption of lymphatics and subsequent lymphedema. To this end, we present the short-term follow-up of a phase II, single-institution, prospectively accrued cohort of patients undergoing ARM.

      Methods

      This institutional review board and Radiation Safety and Monitoring Committee approved this study involving patients undergoing SLNB and/or ALND. Technetium sulfur colloid (∼4 mL) was injected in the subareolar plexus, and ∼5 mL of isosulfan blue dye was injected subcutaneously in the ipsilateral volar surface of the upper extremity (ARM). Data were collected on variations in lymphatic drainage that impacted SLNB or ALND, successful identification and protection of the arm lymphatics, any crossover between a radioactive breast node and a blue ARM node, and occurrence of lymphedema.

      Patients

      Patients undergoing SLNB and/or ALND were enrolled in a prospective, single-arm trial at the Winthrop P. Rockefeller Cancer Institute. The study was approved by the University of Arkansas for Medical Sciences Institutional Review Board. All patients requiring a SLNB or ALND were invited to participate in the study. This is an extension of our ongoing series and fourth publication on this cohort, which began in May 2006.
      • Boneti C.
      • Badgwell B.
      • Robertson Y.
      • Korourian S.
      • Adkins L.
      • Klimberg V.
      Axillary reverse mapping (ARM): initial results of phase II trial in preventing lymphedema after lymphadenectomy.

      Sentinel lymph node procedure

      The SLNB technique has been described in detail in previous studies.
      • Johnson C.B.
      • Boneti C.
      • Korourian S.
      • Adkins L.
      • Klimberg V.S.
      Intraoperative injection of subareolar or dermal radioisotope results in predictable identification of sentinel lymph nodes in breast cancer.
      • Bland K.
      • Klimberg V.S.
      Axillary sentinel lymph node biopsy in mastery techniques in general surgery: breast surgery.
      In brief, a subareolar plexus injection of 1.0 mCi of unfiltered technetium sulfur colloid diluted to a final volume of 4 mL was administered intraoperatively, immediately after induction of general anesthesia. After routine prep and drape, a handheld gamma probe (Neoprobe Corporation, Dublin, OH) was used to localize radioactivity (hot lymph node) before skin incision.

      ARM procedure

      As described previously, most lymphatics from the distal arm enter the axilla along the volar surface of the upper arm.
      • Bland K.
      • Klimberg V.S.
      Axillary reverse mapping in mastery techniques in general surgery: breast surgery.
      There can be alternate anatomy; for example, a branch that courses in the deltopectoral groove can completely bypass the axilla.
      ARM was performed by injecting 5 mL of blue dye deep subcutaneously in the ipsilateral upper inner arm for localization of lymphatics draining the arm.
      • Boneti C.
      • Korourian S.
      • Diaz Z.
      • Santiago C.
      • Mumford S.
      • Adkins L.
      • et al.
      Scientific Impact Award: axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy.
      • Thompson M.
      • Korourian S.
      • Henry-Tillman R.
      • Adkins L.
      • Mumford S.
      • Westbrook K.C.
      • et al.
      Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation.
      • Bland K.
      • Klimberg V.S.
      Axillary lymph node dissection in mastery techniques in general surgery: breast surgery.
      • Guthrie D.
      • Gagnon G.
      The prevention and treatment of postoperative lymphedema of the arm.
      The SLNB was then performed through the mastectomy incision or an incision in the axilla. The ARM procedure always included both radioactivity in the breast as well as blue dye in the arm because, in a small fraction of patients, the ARM node will also be the SLN from the breast.
      • Thompson M.
      • Korourian S.
      • Henry-Tillman R.
      • Adkins L.
      • Mumford S.
      • Westbrook K.C.
      • et al.
      Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation.
      • Boneti C.
      • Badgwell B.
      • Robertson Y.
      • Korourian S.
      • Adkins L.
      • Klimberg V.
      Axillary reverse mapping (ARM): initial results of phase II trial in preventing lymphedema after lymphadenectomy.
      • Bland K.
      • Klimberg V.S.
      Axillary reverse mapping in mastery techniques in general surgery: breast surgery.
      In patients with a heavily positive axilla, the tumor can cause obstruction of the lymphatic drainage and theoretically lead the tumor to flow retrograde into the nodes primarily draining the arm. Dual mapping, 1 from the breast and 1 from the arm, determines the presence of crossover between the breast and arm drainage (Fig 1, Fig 2). Initially when there was crossover, that is, when the ARM node was also the sentinel lymph node (SLN), the ARM node was taken. Later in the study, when ARM nodes were removed, there was a conscious effort made to “reanastomose” the remaining afferent and efferent lymphatics. Their “reanastomosis” is not a lumen-to-lumen anastomosis, but rather a reapproximation of the transected ends of the lymphatic channel.
      Figure thumbnail gr1
      Fig 1Confluence of breast and axillary reverse mapping (ARM) lymphatics typically seen at level III, but variations may place ARM lymphatics within operative field of dissection (level I or II) or in juxtaposition to SLN. RA, Radioactive.
      Figure thumbnail gr2
      Fig 2Blue node seen juxtaposed to radioactive sentinel lymph node (SLN; identified by gamma probe and in Babcock) without crossover and able to be spared. Afferent blue lymphatic seen connecting to blue node as well.

      ALND

      When the SLN was positive and a mastectomy was performed, the ALND was completed through the same incision; otherwise, a separate axillary incision was made. An anatomic resection of level I and II lymph nodes was completed, taking care to identify and preserve blue lymphatics.
      • Bland K.
      • Klimberg V.S.
      Axillary lymph node dissection in mastery techniques in general surgery: breast surgery.
      If the radioactive sentinel node was also a blue node or was suspicious (palpable or via ultrasonography), the ALND included the blue nodes and lymphatics; otherwise, the blue lymphatics and blue nodes were preserved. When possible after removing blue ARM nodes, the remaining afferent and efferent lymphatics were “anastomosed” using 7.0–9.0 prolene.
      • Guthrie D.
      • Gagnon G.
      The prevention and treatment of postoperative lymphedema of the arm.
      This was documented intraoperatively.

      Pathology

      Lymph nodes were sectioned at 3-mm intervals in the long axis unless the lymph node itself was <5 mm, in which case they were bisected. Intraoperative touch-prep cytology was performed followed by permanent section and routine hematoxylin and eosin staining.
      • Rubio I.T.
      • Korourian S.
      • Cowan C.
      • Krag D.N.
      • Colvert M.
      • Klimberg V.S.
      Sentinel lymph node biopsy for staging breast cancer.
      • Henry-Tillman R.S.
      • Korourian S.
      • Rubio I.T.
      • Johnson A.T.
      • Mancino A.T.
      • Massol N.
      • et al.
      Intraoperative touch preparation for sentinel lymph node biopsy: a 4-year experience.
      Lymph nodes from the completion ALND were bisected along the long axis, and 1 section from each node was submitted for hematoxylin and eosin staining.

      Lymphedema assessment

      The measurements of arm volume were obtained by water volume displacement as described previously in our initial series.
      • Thompson M.
      • Korourian S.
      • Henry-Tillman R.
      • Adkins L.
      • Mumford S.
      • Westbrook K.C.
      • et al.
      Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation.
      • Bland K.
      • Klimberg V.S.
      Axillary lymph node dissection in mastery techniques in general surgery: breast surgery.
      Briefly, a mark was placed 10 cm proximal from the lateral epicondyle. The arm was then inserted into a cylinder filled with water up to the mark on the arm. The water displacement was recorded at baseline and every 6 months over a 4-year follow-up period. The arm volume of the contralateral arm was measured similarly as a control for weight gain or loss. The arm volume increase was obtained by subtracting the volume change on the contralateral side from the volume change on the affected side using the formula [(affected current volume − affected baseline volume)/(affected baseline volume) × 100] − [(contralateral current volume − contralateral baseline volume)/(contralateral baseline volume) × 100]. This protocol is based on the same protocol used for the NSABP B 32 Protocol for arm volume measurements.
      • Ashikaga T.
      • Krag D.N.
      • Land S.R.
      • Julian T.B.
      • Anderson S.J.
      • Brown A.M.
      • et al.
      Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection.
      Based on the consensus document of the International Society of Lymphology, an arm volume increase of the affected side over the opposite side of ≥20% was considered lymphedema.
      • Földi M.
      Remarks concerning the consensus document (CD) of the International Society of Lymphology “The diagnosis and treatment of peripheral lymphedema”.

      Statistics and data

      Data were collected in a prospective database in Microsoft Excel (Microsoft Corporation, Redmond, WA) on identification rate, variations in lymphatic drainage, ARM lymphatics preservation rate, nodal status, and lymphedema rate at 6-month intervals. Results were examined with descriptive analysis utilizing SigmaPlot (Systat Software Inc, San Jose, CA).

      Results

      Study population

      The 360 patients included in the study underwent standard operative treatment for the primary breast cancer (ie, lumpectomy or mastectomy) and axillary staging, including SLNB alone, SLNB followed by ALND, and ALND only. Their average age was 56 years. Of 336 invasive cancers, 67% (225/336) were T1 lesions, 24.4% (80/336) T2, and 6.5% (22/336) T3. In 9 cases (2.7%), the size of the tumor could not be assessed accurately. Patients with metastatic axillary disease had N1 disease in 76.1% (83/109), N2 disease in 15.5% (17/109), and N3 disease in 8.2% (9/109).
      The mean ± standard deviation follow-up was 12.0 ± 13.6 months for all 360 patients. Only 9 patients (2.5%) were lost to follow-up; 11 died during the study. A total of 122 patients had the operative procedure done recently, and no follow-up information is available. The remaining 238 patients had an average follow-up of 18 months (range, 3–48) and were used in the analyses for lymphedema outcome. The 20 patients lost to follow-up or deceased were included only in the analyses regarding the anatomy and blue nodes involved by malignancy.

      Operative procedure

      A total of 348 patients underwent a SLNB. Of those, 237 of 348 (68.1%) had a SLNB only and 111 of 348 (31.9%) went on to an ALND owing to a positive axilla. An additional 12 of 360 patients (3.3%) had ALND owing to a clinically positive axilla/preoperative core needle biopsy.

      Anatomy

      Blue lymphatics were identified in 80 of 237 SLN incisions (33.7%) and 93 of 123 ALND incisions (75.4%). In 96% of patients with SLNB (334/348), breast SLNs were hot but not blue. Crossover (SLN hot and blue) was seen in 15/348 SLN procedures (4.3%). Blue nodes were found to be juxtaposed yet separate in 36 of 360 (10%) overall, which would place them at risk of injury. When blue lymphatics were seen within the SLN bed, the blue ARM node was juxtaposed to the SLN in 28 of 80 (35%). Anatomic variations seen included above or below the axillary vein, slings, and aprons. Even in patients in whom a blue node was resected, there were cases where additional blue lymphatics visualized within the wound were able to be spared.

      Pathology

      Of the resected ARM nodes, 5 of 27 (18.5%) contained tumor. Two of these ARM nodes were in cases of crossover with 1 each being yN1 and N2 disease. The other 3 cases were palpable or entrapped nodes in heavily positive axilla (N2 or N3) without crossover. Of the 4% of cases where crossover (concordant with SLN) was identified and nodes resected, 2 of 15 (14.3%) contained malignancy. Of the blue-only nodes resected, 3 of 12 (25%) were positive. Of the total 96% nonconcordant axilla, 3 of 345 blue nodes (0.9%) were involved by malignancy, all in heavily positive axilla. Of the transected ARM lymphatics, the lymphatics were anastomosed in 3 patients. One lymphatic was partially avulsed during dissection. The other 2 were clinically positive/not hot, blue nodes (N1; 3 of 8 and 4 of 26).

      Lymphedema

      Overall, 20 of 238 patients (8.4%) undergoing SLNB and/or ALND either experienced an objective finding of lymphedema or were treated for lymphedema based on subjective symptoms. Objective findings of volume difference were seen in 7 of 238 (2.9%). Two patients had an objective volume difference measured earlier in follow-up that has since improved, although they never experienced any symptoms subjectively. Another 5 patients had objective findings at their last follow-up, but only 3 experienced symptoms and sought treatment. A total of 13 patients experienced subjective symptoms of lymphedema for which they were treated, but they either showed no difference in objective volume or did not meet the threshold for volume increase for what was considered lymphedema.
      • Földi M.
      Remarks concerning the consensus document (CD) of the International Society of Lymphology “The diagnosis and treatment of peripheral lymphedema”.
      Of those patients with objective findings of lymphedema, we found a SLNB lymphedema rate of 2.5% (4/158) and ALND of 3.7% (3/80). Specifically looking at the group of patients in whom blue lymphatics were able to be identified and preserved, we found a SLNB lymphedema rate of 1.7% (1/58) and ALND of 4.8% (3/62). In those patients in whom an identified blue lymphatic was transected, there was a 4.5% rate of lymphedema (1/22). That patient has since improved with treatment. In the patients in whom there were no blue lymphatics identified in the surgical field, the incidence of lymphedema was 2.1% (2/94). The use of the 20% volume change was based on an effort to report our data in a manner that would allow comparison with other groups/studies. When we apply the Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events (CTEP) grading system to evaluate those patients with smaller volumetric differences and differentiate how many of our patients experienced greater degrees of severity as a percentile of the lymphedema group, we note that of the SLN patients who developed lymphedema, 5% were grade 3, 35% grade 2, and 60% grade 1. Of the ALND patients, 5% were grade 3, 50% grade 2, and 45% grade 1. Using ARM, we had only 3 patients who experienced grade 3 lymphedema, which underscores the utility of the technique.

      Cancer Therapy Evaluation Program. Common terminology criteria for adverse events, version 3.0 [updated 2003 Mar 31; revised 2006 Aug 9]. Available from: http://ctep.cancer.gov.

      Of those patients in whom blue lymphatics were preserved and lymphedema was found, the SLN case demonstrated lymphedema at 18 months, whereas the ALNDs cases demonstrated lymphedema at 6 and 12 months (×2). Of the 3 patients in whom the blue lymphatics were reanastomosed, there were no cases of lymphedema.

      Recurrence

      Blue lymphatics were identified in 173 patients; these lymphatics were able to be preserved in 137 of 173 cases (79.2%) in which they were identified. In this group there were 11 distant recurrences among 173 patients (6.4%) and 2 local recurrences (1.2%). There was 1 axillary recurrence over an average follow-up of 12 months, which was found at 17 months of follow-up in a patient in whom blue dye was not identified and therefore no blue nodes were preserved.

      Discussion

      This phase II study represents the largest series reported to date on ARM and the only one demonstrating the effectiveness of the ARM procedure in preventing lymphedema. We showed many anatomic variations that were well below (caudal to) the axillary vein, the traditional superior border of an ALND.
      • Klimberg S.
      • Townsend C.
      • Evers M.
      Axillary reverse mapping. Atlas of breast surgical techniques.
      The most consistent drainage was to the lymph node just below the vein and just on or lateral to the tendon of the latissimus dorsi muscle, followed by the sling, the apron, and those surrounding the axillary vein. The apron required the most tedious dissection to separate and spare uninvolved ARM lymphatics. This cohort of patients experienced an overall lymphedema rate of 8.4% (20/238), including both objective findings of lymphedema as well as subjective symptoms. Objective findings of volume difference were seen in 7 of 238 (2.9%), and another 13 patients experienced subjective symptoms but showed no objective volume difference or did not meet the threshold volume increase for what was considered lymphedema.
      • Földi M.
      Remarks concerning the consensus document (CD) of the International Society of Lymphology “The diagnosis and treatment of peripheral lymphedema”.
      Some of these complaints of “lymphedema” resolved with treatment of pain issues, indicating that patients have heard of lymphedema but do not understand what is really meant by lymphedema. In addition, of the 3 patients in whom the lymphatics were transected and reanastomosed, there were no cases of objective or subjective lymphedema.
      In our original study,
      • Thompson M.
      • Korourian S.
      • Henry-Tillman R.
      • Adkins L.
      • Mumford S.
      • Westbrook K.C.
      • et al.
      Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation.
      blue nodes were removed routinely; the contrast with this study is that we only removed them if they had crossover or appeared abnormal. Others have shown rates of metastatic involvement of blue nodes between 14 and 43% and almost exclusively in patients with N2 or N3 disease (Table). Of note, these investigators did not use our described technique of dual mapping where radioactivity is used to map the breast and blue dye to map the arm (Table). Notably, Kang et al
      • Kang S.H.
      • Choi J.E.
      • Jeon Y.S.
      • et al.
      Preservation of lymphatic drainage from arm in breast cancer surgery: Is it safe?.
      used our described dual mapping technique and had similar results demonstrating that nodes with blue dye alone are rarely positive. Kang et al reported a 36% rate of malignancy in the blue nodes with crossover and only 1.3% in nonconcordant axilla. In our study, 5 of 27 resected ARM nodes (18.5%) contained tumor. Two of these ARM nodes were in cases of crossover with N1 and N2 disease. The other 3 cases were nonconcordant in palpable or entrapped nodes in a heavily positive axilla (N2 or N3) without crossover. We therefore found a 14.3% rate of malignancy (2/15) in the concordant cases and only 0.9% (3/334) in nonconcordant but heavily positive axilla. Currently, all of these nodes would be resected and reanastomosed.
      TableSummary of ARM publications
      StudyNo. of patientsSLNBALNDBlue lymphatics or nodes IDNo. of nodes resectedARM nodes removedARM nodes +Crossover
      Thompson et al
      • Thompson M.
      • Korourian S.
      • Henry-Tillman R.
      • Adkins L.
      • Mumford S.
      • Westbrook K.C.
      • et al.
      Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation.
      40361861% (11/18) with ALND12.5700
      Nos et al
      • Nos C.
      • Kaufmann G.
      • Clough K.B.
      • Collignon M.A.
      • Zerbib E.
      • Cusumano P.
      • et al.
      Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection.
      232391% (21/23)10.71.6 (21 cases)14% (3/21) all in ≥9; radioactivity to ID ARM + blue dye in node
      Kang et al
      • Kang S.H.
      • Choi J.E.
      • Jeon Y.S.
      • et al.
      Preservation of lymphatic drainage from arm in breast cancer surgery: Is it safe?.
      1291244871.6% (58/81) SLN field

      89.5% (43/48) ALND
      1.5 (96 SLNB and 5 ALND)36% (7/19) when there is crossover; 1.3% (1/77) in nonconcordant axilla18.9% (19/96)
      Casabona et al
      • Casabona F.
      • Bogliolo S.
      • Valenzano Menada M.
      • Sala P.
      • Villa G.
      • Ferrero S.
      Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients.
      7272937.5% (27/72) in the SLN fieldSLNB 1.33 nodes0
      88.9% (8/9) in ALNDALND 16
      Boneti et al
      • Boneti C.
      • Korourian S.
      • Diaz Z.
      • Santiago C.
      • Mumford S.
      • Adkins L.
      • et al.
      Scientific Impact Award: axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy.
      2202144040.6% (87/214) in the SLN field12.71502.8% (6/214)
      Ponzone et al
      • Ponzone R.
      • Cont N.T.
      • Maggiorotto F.
      • Cassina E.
      • Mininanni P.
      • Biglia N.
      • et al.
      Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer.
      496/4949

      43 Ø Tc
      73.5% (34/49) ID blue lymphatics

      55.1% (27/49) ID blue nodes
      27 cases3 cases (18, 18, and ≥7 LN)
      Noguchi et al
      • Noguchi M.
      • Yokoi M.
      • Nakano Y.
      Axillary reverse mapping with indocyanine fluorescence imaging in patients with breast cancer.
      20128ALND 88% (7/8); SLNB 75% (9/12)23All cases average, 2.7None in the SLN group; 43% of ALND (3/8) (3, 13, ≥14 LN), no isotope14% (2/14)
      Bedrosian et al
      • Bedrosian I.
      • Babiera G.V.
      • Mittendorf E.A.
      • Kuerer H.M.
      • Pantoja L.
      • Hunt K.K.
      • et al.
      A phase I study to assess the feasibility and oncologic safety of axillary reverse mapping in breast cancer patients.
      303070% (21/30) lymphatic; 50% (15/30) nodes261 av18% (2/11 with metastases); no isotope used to detect crossover
      Ochoa, present study36023712380/237 (33.7%) SLN; 93/123 (75.4%) ALND27 cases5/27 (18.5%)4.3% (15/348)
      ALND, Axillary lymph node dissection; ARM, axillary reverse mapping; ID, identify; LN, lymph node; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy.
      Furthermore, only 1 axillary recurrence was seen, and occurred in a patient in whom blue dye was not identified; therefore, no blue nodes were specifically left behind. This recurrence was found 17 months after modified radical mastectomy for yT2 (4 cm) N1 (3/7) disease. When found, the patient had metastatic disease present within her liver. The finding that when blue lymphatics were spared in this fairly large trial with an average of 12 months of follow-up is a surrogate for the safety of ARM despite leaving blue, nonradioactive nodes lymph nodes in the axilla. This is important because patients with ≥4 positive nodes receive XRT.
      There are ∼240,000 cases of breast cancer per year and an extant total of 3–5 million cases of lymphedema in the United States, making this among the most clinically important postoperative problems.
      • Rockson S.G.
      • Rivera K.K.
      Estimating the population burden of lymphedema.
      Reports on the incidence of lymphedema vary with measurement technique, duration of follow-up, time to measurement, use of XRT, and extent of operation.
      Symptoms of lymphedema may present within days or ≤30 years later; although 80% present within 3 years of operation, with the remainder at a rate of 1% per year.
      • Petrek J.A.
      • Senie R.T.
      • Peters M.
      • et al.
      Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.
      • Shaw C.
      • Mortimer P.
      • Judd P.A.
      Randomized controlled trial comparing a low-fat diet with a weight-reduction diet in breast cancer-related lymphedema.
      Volume displacement is the gold standard for measurement, because subjective symptoms of pain or discomfort are often mistaken for lymphedema. SLNB was developed in an effort to prevent the high morbidity seen with ALND; however, cooperative group trials have still shown lymphedema rates of approximately 5–8% with SLN biopsy alone.
      • Ashikaga T.
      • Krag D.N.
      • Land S.R.
      • Julian T.B.
      • Anderson S.J.
      • Brown A.M.
      • et al.
      Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection.
      In the American College of Surgeons Oncology Group Z0010 prospective observational study,
      • Wilke L.G.
      • McCall L.M.
      • Posther K.E.
      • Whitworth P.W.
      • Reintgen D.S.
      • Leitch A.M.
      • et al.
      Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial.
      lymphedema defined as a change in arm circumference of >2 cm compared with the contralateral or control arm and with baseline measurements occurred at a rate of nearly 7%. Multiple comparison studies, several of which were randomized, have confirmed less morbidity and lymphedema rates for SLNB when compared with ALND. Lymphedema in ALND groups ranged from 13 to 77%, varying with how closely lymphedema was monitored, duration of follow-up,
      • Schrenk P.
      • Rieger R.
      • Shamiyeh A.
      • et al.
      Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.
      • Blanchard D.K.
      • Donohue J.H.
      • Reynolds C.
      • et al.
      Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer.
      • Schijven M.P.
      • Vingerhoets A.J.
      • Rutten H.J.
      • et al.
      Comparison of morbidity between axillary lymph node dissection and sentinel node biopsy.
      • Ronka R.
      • von Smitten K.
      • Tasmuth T.
      • et al.
      One-year morbidity after sentinel node biopsy and breast surgery.
      • Leidenius M.
      • Leivonen M.
      • Vironen J.
      • von Smitten K.
      The consequences of long-time arm morbidity in node-negative breast cancer patients with sentinel node biopsy or axillary clearance.
      questionably the number of positive lymph nodes,
      • Albert U.S.
      • Koller M.
      • Kopp I.
      • Lorenz W.
      • Schulz K.D.
      • Wagner U.
      Early self-reported impairments in arm functioning of primary breast cancer patients predict late side effects of axillary lymph node dissection: results from a population-based cohort study.
      postoperative irradiation,
      • Larson D.
      • Weinstein M.
      • Goldberg I.
      • et al.
      Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy.
      extent of operation, body habitus, and a number of other patient characteristics.
      • Ashikaga T.
      • Krag D.N.
      • Land S.R.
      • Julian T.B.
      • Anderson S.J.
      • Brown A.M.
      • et al.
      Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection.
      • Nos C.
      • Kaufmann G.
      • Clough K.B.
      • Collignon M.A.
      • Zerbib E.
      • Cusumano P.
      • et al.
      Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection.
      • Hayes S.C.
      • Janda M.
      • Cornish B.
      • Battistutta D.
      • Newman B.
      Lymphedema after breast cancer: Incidence, risk factors and effect of upper body.
      Although the rate of lymphedema was much less with the SLNB, it remained clinically significant (range, 0–13%) and NSABP B-32 found lymphedema with SLNB to be ∼8%.
      • Ashikaga T.
      • Krag D.N.
      • Land S.R.
      • Julian T.B.
      • Anderson S.J.
      • Brown A.M.
      • et al.
      Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection.
      Thus, SLNB has improved but not abolished the problem of lymphedema. Our group placed 97 patients on the B-32 protocol. Our rate of lymphedema was 8% for SLNB and 23% for ALND on B-32. The exact lymphedema measurement schedule and protocol was used for the present study, and lymphedema rates with ARM are sequentially comparable with and improved over our B-32 rates.
      Surprisingly, just as many women get lymphedema from a negative SLNB as all those who undergo ALND. Even though the rate of lymphedema from SLNB is only about one third of that with ALND, the number of SLNBs performed is approximately 3-fold that of ALND. In the present study, a blue lymphatic was seen in 80 of 237 SLNB-only procedures. In 7 of these SLNB-only (small incision) procedures, crossover was identified; therefore, in 73 of the 237 (30.8%), a blue lymphatic was identified that would otherwise have been in harm's way in a negative axilla. These are the cases in which we consider it to be most useful, so that patients who do not even have axillary disease are not placed at an unnecessary risk. There is need for an improved method of SLNB as well as ALND. The technique of ALND is variable in practice, but the basic anatomic principles have not changed in decades. Surgeons do not need necessarily to stop doing ALNDs for positive lymph nodes, but rather to change the principles and technique of how to perform them. Therefore, we hypothesized that we could decrease the rate of lymphedema for both SLNB and ALND using the technique of ARM. ARM allows us to identify lymphatics that are in the surgical field but primarily drain the upper extremity. By identifying and avoiding transection of these lymphatics, we are able to further minimize the morbidity of these procedures, while not compromising our oncologic resection.

      References

        • Ivens D.
        • Hoe A.L.
        • Podd T.J.
        • Hamilton C.R.
        • Taylor I.
        • Royle G.T.
        Assessment of morbidity from complete axillary dissection.
        Br J Cancer. 1992; 66: 136-138
        • Somers R.G.
        • Jablon L.K.
        • Kaplan M.J.
        • Sandler G.L.
        • Rosenblatt N.K.
        The use of closed suction drainage after lumpectomy and axillary node dissection for breast cancer. A prospective randomized trial.
        Ann Surg. 1992; 215: 146-149
        • Passik S.D.
        • McDonald M.V.
        Psychosocial aspects of upper extremity lymphedema in women treated for breast carcinoma.
        Cancer. 1998; 83: 2817-2820
        • Tobin M.B.
        • Lacey H.J.
        • Meyer L.
        • Mortimer P.S.
        The psychosocial morbidity of breast cancer-related arm swelling. Psychological morbidity of lymphedema.
        Cancer. 1993; 72: 3248-3252
        • McMasters K.M.
        • Giuliano A.E.
        • Ross M.I.
        • Reintgen D.S.
        • Hunt K.K.
        • Byrd D.R.
        • et al.
        Sentinel-lymph-node biopsy for breast cancer–not yet the standard of care.
        N Engl J Med. 1998; 339: 990-995
        • Leidenius M.
        • Leppanen E.
        • Krogerus L.
        • et al.
        Motion restriction and axillary web syndrome after sentinel node biopsy and axillary clearance in breast cancer.
        Am J Surg. 2003; 185: 127-130
        • Burak W.E.
        • Hollenbeck S.T.
        • Zervos E.E.
        • et al.
        Sentinel lymph node biopsy results in less post operative morbidity compared with axillary lymph node dissection for breast cancer.
        Am J Surg. 2002; 183: 23-27
        • Swenson K.K.
        • Nissen M.J.
        • Ceronsky C.
        • et al.
        Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer.
        Ann Surg Oncol. 2002; 9: 745-753
        • Rubio I.T.
        • Korourian S.
        • Cowan C.
        • Krag D.N.
        • Colvert M.
        • Klimberg V.S.
        Sentinel lymph node biopsy for staging breast cancer.
        Am J Surg. 1998; 176: 532-537
        • Kissin M.W.
        • della Rovere Q.G.
        • Easton D.
        • Westbury G.
        Risk of lymphedema following the treatment of breast cancer.
        Br J Surg. 1986; 73: 580-584
        • Delouche G.
        • Bachelot F.
        • Premont M.
        • Kurtz J.M.
        Conservation treatment of early breast cancer: long term results and complications.
        Int J Radiat Oncol Biol Phys. 1987; 13: 29-34
        • Larson D.
        • Weinstein M.
        • Goldberg I.
        • et al.
        Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy.
        Int J Radiat Oncol Biol Phys. 1986; 12: 1575-1582
        • Petrek J.A.
        • Senie R.T.
        • Peters M.
        • et al.
        Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis.
        Cancer. 2001; 92: 1368-1377
        • Velanovich V.
        • Szymanski W.
        Quality of life of breast cancer patients with lymphedema.
        Am J Surg. 1999; 177: 184-187
        • Kwan W.
        • Jackson J.
        • Weir L.M.
        • et al.
        Chronic arm morbidity after curative breast cancer treatment: prevalence and impact on quality of life.
        J Clin Oncol. 2002; 20: 4242-4248
        • Silberman A.W.
        • McVay C.
        • Cohen J.S.
        • et al.
        Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique: implications for patients with breast cancer.
        Ann Surg. 2004; 240: 1-6
        • Haid A.
        • Köberle-Wührer R.
        • Knauer M.
        • et al.
        Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation.
        Breast Cancer Res Treat. 2002; 73: 31-36
        • Wilke L.G.
        • McCall L.M.
        • Posther K.E.
        • Whitworth P.W.
        • Reintgen D.S.
        • Leitch A.M.
        • et al.
        Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial.
        Ann Surg Oncol. 2006; 13: 491-500
        • Schrenk P.
        • Rieger R.
        • Shamiyeh A.
        • et al.
        Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.
        Cancer. 2000; 88: 608-614
        • Blanchard D.K.
        • Donohue J.H.
        • Reynolds C.
        • et al.
        Relapse and morbidity in patients undergoing sentinel lymph node biopsy alone or with axillary dissection for breast cancer.
        Arch Surg. 2003; 138: 482-488
        • Schijven M.P.
        • Vingerhoets A.J.
        • Rutten H.J.
        • et al.
        Comparison of morbidity between axillary lymph node dissection and sentinel node biopsy.
        Eur J Surg Oncol. 2003; 29: 341-350
        • Ronka R.
        • von Smitten K.
        • Tasmuth T.
        • et al.
        One-year morbidity after sentinel node biopsy and breast surgery.
        Breast. 2005; 14: 28-36
        • Leidenius M.
        • Leivonen M.
        • Vironen J.
        • von Smitten K.
        The consequences of long-time arm morbidity in node-negative breast cancer patients with sentinel node biopsy or axillary clearance.
        J Surg Oncol. 2005; 92: 23-31
        • Klimberg S.
        • Townsend C.
        • Evers M.
        Axillary reverse mapping. Atlas of breast surgical techniques.
        Saunders, New York2010: 174-181
        • Mansel R.
        • Fallowfield L.
        • Kissin M.
        • et al.
        Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial.
        J Natl Cancer Inst. 2006; 98: 599-609
        • Tengrup I.
        • Tennvall-Nittby L.
        • Christiansson I.
        • et al.
        Arm morbidity after breast-conserving therapy for breast cancer.
        Acta Oncol. 2000; 39: 393-397
        • Werner R.S.
        • McCormick B.
        • Petrek J.A.
        • et al.
        Arm edema in conservatively managed breast cancer: obesity is a major predictive factor.
        Radiology. 1991; 180: 177-184
        • Harlow S.P.
        • Krag D.N.
        sentinel lymph node – why study it: implications of the B-32 Study.
        Semin Surg Oncol. 2001; 20: 224-229
      1. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Available from: http://seer.cancer.gov/faststats/sites.php?site=Breast%20Cancer&stat=Incidence.

        • Sakorafas G.H.
        • Peros G.
        • Cataliotti L.
        • et al.
        Lymphedema following axillary lymph node dissection for breast cancer.
        Surg Oncol. 2006; 15: 153-165
        • Giuliano A.E.
        • Hunt K.K.
        • Ballman K.V.
        • Beitsch P.D.
        • Whitworth P.W.
        • Blumencranz P.W.
        • et al.
        Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.
        JAMA. 2011; 305: 569-575
        • Burnett A.F.
        • Stone P.J.
        • Klimberg S.V.
        • Gregory J.L.
        • Roman J.R.
        Lower extremity glandography (LEG): a new concept to identify and enhance lymphatic preservation.
        Int J Gynecol Cancer. 2011; 21: 582-586
        • Boneti C.
        • Korourian S.
        • Diaz Z.
        • Santiago C.
        • Mumford S.
        • Adkins L.
        • et al.
        Scientific Impact Award: axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy.
        Am J Surg. 2009; 198: 482-487
        • Thompson M.
        • Korourian S.
        • Henry-Tillman R.
        • Adkins L.
        • Mumford S.
        • Westbrook K.C.
        • et al.
        Axillary reverse mapping (ARM): a new concept to identify and enhance lymphatic preservation.
        Ann Surg Oncol. 2007; 14: 1890-1895
        • Boneti C.
        • Badgwell B.
        • Robertson Y.
        • Korourian S.
        • Adkins L.
        • Klimberg V.
        Axillary reverse mapping (ARM): initial results of phase II trial in preventing lymphedema after lymphadenectomy.
        Minerva Ginecol. 2012; 64: 421-430
        • Johnson C.B.
        • Boneti C.
        • Korourian S.
        • Adkins L.
        • Klimberg V.S.
        Intraoperative injection of subareolar or dermal radioisotope results in predictable identification of sentinel lymph nodes in breast cancer.
        Ann Surg. 2011; 254: 612-618
        • Bland K.
        • Klimberg V.S.
        Axillary sentinel lymph node biopsy in mastery techniques in general surgery: breast surgery.
        Lippincott, Williams & Wilkins, Philadelphia2011: 155-169
        • Bland K.
        • Klimberg V.S.
        Axillary reverse mapping in mastery techniques in general surgery: breast surgery.
        Lippincott, Williams & Wilkins, Philadelphia2011: 201-208
      2. Földi M. Földi E. Földi's textbook of lymphology: for physicians and lymphedema therapists. 2nd edition. Mosby Elsevier, New York2006
        • Bland K.
        • Klimberg V.S.
        Axillary lymph node dissection in mastery techniques in general surgery: breast surgery.
        Lippincott, Williams & Wilkins, New York2011: 183-200
        • Guthrie D.
        • Gagnon G.
        The prevention and treatment of postoperative lymphedema of the arm.
        Ann Surg. 1946; 123: 925-935
        • Henry-Tillman R.S.
        • Korourian S.
        • Rubio I.T.
        • Johnson A.T.
        • Mancino A.T.
        • Massol N.
        • et al.
        Intraoperative touch preparation for sentinel lymph node biopsy: a 4-year experience.
        Ann Surg Oncol. 2002; 9: 333-339
        • Ashikaga T.
        • Krag D.N.
        • Land S.R.
        • Julian T.B.
        • Anderson S.J.
        • Brown A.M.
        • et al.
        Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection.
        J Surg Oncol. 2010; 102: 111-118
        • Földi M.
        Remarks concerning the consensus document (CD) of the International Society of Lymphology “The diagnosis and treatment of peripheral lymphedema”.
        Lymphology. 2004; 37: 168-173
      3. Cancer Therapy Evaluation Program. Common terminology criteria for adverse events, version 3.0 [updated 2003 Mar 31; revised 2006 Aug 9]. Available from: http://ctep.cancer.gov.

        • Kang S.H.
        • Choi J.E.
        • Jeon Y.S.
        • et al.
        Preservation of lymphatic drainage from arm in breast cancer surgery: Is it safe?.
        Cancer Res. 2009; 69: 201
        • Rockson S.G.
        • Rivera K.K.
        Estimating the population burden of lymphedema.
        Ann N Y Acad Sci. 2008; 1131: 147-154
      4. Foldi M. Foldi E. Foldi's textbook of lymphology for physicians and lymphedema therapists. Mosby Elsevier, Maryland Heights (MO)2006
        • Shaw C.
        • Mortimer P.
        • Judd P.A.
        Randomized controlled trial comparing a low-fat diet with a weight-reduction diet in breast cancer-related lymphedema.
        Cancer. 2007; 109: 1949-1956
        • Albert U.S.
        • Koller M.
        • Kopp I.
        • Lorenz W.
        • Schulz K.D.
        • Wagner U.
        Early self-reported impairments in arm functioning of primary breast cancer patients predict late side effects of axillary lymph node dissection: results from a population-based cohort study.
        Breast Cancer Res Treat. 2006; 100: 285-292
        • Hayes S.C.
        • Janda M.
        • Cornish B.
        • Battistutta D.
        • Newman B.
        Lymphedema after breast cancer: Incidence, risk factors and effect of upper body.
        J Clin Oncol. 2008; 26: 3536-3542
        • Nos C.
        • Kaufmann G.
        • Clough K.B.
        • Collignon M.A.
        • Zerbib E.
        • Cusumano P.
        • et al.
        Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection.
        Ann Surg Oncol. 2008; 15: 2550-2555
        • Casabona F.
        • Bogliolo S.
        • Valenzano Menada M.
        • Sala P.
        • Villa G.
        • Ferrero S.
        Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients.
        Ann Surg Oncol. 2009; 16: 2459-2463
        • Ponzone R.
        • Cont N.T.
        • Maggiorotto F.
        • Cassina E.
        • Mininanni P.
        • Biglia N.
        • et al.
        Extensive nodal disease may impair axillary reverse mapping in patients with breast cancer.
        J Clin Oncol. 2009; 27: 5547-5551
        • Noguchi M.
        • Yokoi M.
        • Nakano Y.
        Axillary reverse mapping with indocyanine fluorescence imaging in patients with breast cancer.
        J Surg Oncol. 2010; 101: 217-221
        • Bedrosian I.
        • Babiera G.V.
        • Mittendorf E.A.
        • Kuerer H.M.
        • Pantoja L.
        • Hunt K.K.
        • et al.
        A phase I study to assess the feasibility and oncologic safety of axillary reverse mapping in breast cancer patients.
        Cancer. 2010; 116: 2543-2548