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Clinical feasibility of Axillary Reverse Mapping and its influence on breast cancer related lymphedema: a systematic review
contralateral prophylactic mastectomy. J Clin Oncol. 2011;29: 2158-2164. 5. Cody HS 3rd. Routine contralateral breast biopsy: helpful or irrelevant?
Clinical feasibility of Axillary Reverse Mapping and its influence on breast cancer related lymphedema: a systematic review
Experience in 871 patients, 19791993. Ann Surg. 1997;225:370-376. 6. McLaughlin SA, Stempel M, Morris EA, Liberman L, King TA. Can magnetic resonance imaging be
Eur J Obstet Gynecol Reprod Biol 200:117-122, 2016
until May 13, 2015. The level of evidence of these studies was low (mostly level 3). Therefore the conclusions are that the ARM procedure is feasible although ARM-node rates have a broad range. Additionally, from a theoretical point there is a clear benefit from ARM in terms of lymphedema prevention. From a practical point there is little scientific data to support this due to the lack of studies; and especially because of the different methods and definitions for lymphedema used in the different studies.
Breast cancer is the most common malignancy in women worldwide. Fortunately, the overall survival is good. Therefore it is important to focus on the morbidities related to breast cancer treatment. One of the most dreaded morbidities is lymphedema. In 2007 the Axillary Reverse Mapping (ARM) was introduced to limit the invasiveness in the axilla during breast cancer surgery. It is hypothesized that ARM is able to limit the incidence of breast cancer related lymphedema (BCRL) considerably. This systematic review aims to answer the following research questions: (1) which approaches for ARM are described? (2) Is ARM surgical feasible and oncological safe? (3) Does ARM decrease the incidence of lymphedema after sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND)? In total 27 papers were retrieved using four electronic databases (PubMed, Web of Science, Medline and Cochrane clinical trials; assessed
As one can see from this welldone and thorough systematic review by Gebruers and Tjalma, the incidence of BCRL varies widely depending on the surgery performed, who is performing it, the measurement technique, and the timing. The fact that surgeons doing supposedly the same operation, whether it is an SLNB or ALND, have lymphedema rates from 0% to 13% and 7% to 77%, respectively, gives rise to the hope that refining our technique may help prevent lymphedema. As practiced around the world, the technique of ALND, and even SLNB, is not standardized, compromising the staging of and recurrence in the axilla as well as the risk of lymphedema. Some may surmise that the risk of lymphedema with SLNB is low already, but remember that most lymphedema after an SLNB occurs from a negative SLNB, which ultimately has no benefit to the patient. In reality, today, just as many women per 100 who undergo an
Gebruers N, Tjalma WAA (Dept of Rehabilitation Sciences and Physiotherapy, Wilrijk, Belgium; Faculty of Medicine and Health Sciences, Wilrijk, Belgium; et al)
used to select patients for sentinel lymph node biopsy in prophylactic mastectomy? Cancer. 2008;112: 1214-1221.
axillary surgery develop lymphedema from an SLNB as from an ALND. This is true in that although the rate of BCRL is lower in SLNB than in ALND, many more women will undergo an SLNB for breast cancer staging. In addition, the burden of lymphedema from the patient’s perspective is quite significant, with many patients fearing BCRL more than a mastectomy. In summary, we need a better surgery. When Fo¨ldi first described the lymphatic drainage of the upper extremity, he carefully detailed which part of the arm drained in which direction, with the bulk of the drainage coalescing in the upper volar surface of the arm, from which it then drained into the axilla. However, once in the axilla, he did not delineate the drainage further, just labeling axillary lymph nodes as such. In fact, when in the axilla, nodes appear the same whether draining the breast, the back, or the upper extremity. Our group has hypothesized that BCRL developed in large part from surgical disruption of the lymphatics.1 Therefore, split mapping of the arm and the breast could delineate which lymph nodes should be taken and which should be spared. We first described the feasibility of this approach, coined the term ARM, and described the variations of ARM lymphatics, some of which draped very low in the axilla. Unfortunately, most who have tried to substantiate our work as detailed in this article have not used split mapping, as we first specified for the ARM
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
287
procedure, but only lymphangiography of the upper extremity.1 As we first reported, there is at least 4% crossover, such that it is important to know when this happens, for then the ARM node is the sentinel lymph node, and we would expect a high rate of positivity when ARM is performed on all comers. When this crossover happens, then the ARM nodes should be resected as a sentinel lymph node. We have looked at how often the ARM node is positive when there is not crossover with the breast lymphatics; it is not often, and it has been reported only when N2 disease is present, in which case these patients would receive radiation. We have recently reported our prospective phase II cumulative experience in 654
patients.1 Our lymphedema rate was less than 1% for SLNB and 6% for ALND. Yue and colleagues2 reported the only small randomized trial in ALND patients that shows a similar BCRL rate of 6% with ARM versus 33% without ARM.2 In the last several years, we have been dissecting the afferent and efferent lymphatics of any nodes to be removed and have reanastomosed/re-approximated lymphatics, and, with a short follow-up, we reported no lymphedema in 81 patients.1 ARM is a feasible procedure when done properly. We long ago proposed and are now shepherding a large prospective randomized protocol through the cooperative group mech-
anism that will help determine the safety and efficacy of this technique.
Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors: A Danish Population-Based Retrospective Study
logical grade, surgical treatment, margin size, and local recurrence were collected from the national Danish Pathology Register. Results.dA total of 479 cases were identified; 354 benign (74%), 89 borderline (19%), 6 uncertain histological grading (1.2%), and 30 possibly PT (6%). The mean age at presentation was 45.6 years (range 18e85), the mean tumor size was 3.5 cm (range 0.5e21), and the mean follow-up time was 98 months (range 1.1e192). We identified 30 local recurrences, i.e., a recurrence rate of 6.3%. Twenty-three recurrences had similar or lower histological grading than the primary tumor, one primary benign PT recurred as a tumor with unclear diagnosis, and one primary borderline PT recurred as malignant. The number of recurrences was too low, and the information on the size of the closest resection margin was too sparse to estimate an adequate margin size for excision of nonmalignant PTs.
Conclusions.dThe recurrence rate of PTs was considerably lower than previously stated in literature. No apparent pattern of progression in histological grading was found. The results do not justify wide excision margins of nonmalignant phyllodes tumors of the breast.
Borhani-Khomani K, Talman M-LM, Kroman N, et al (Univ of Copenhagen, København N, Denmark; Copenhagen Univ Hosp, København Ø, Denmark) Ann Surg Oncol 23:1543-1548, 2016
Purpose.dTo determine the recurrence rate of benign and borderline phyllodes tumors (PTs) of the breast, the association between the size of resection margin and risk of recurrence and the risk of progression of histological grading at recurrence. Methods.dNationwide retrospective study on Danish women aged 18 years or older, operated from 1999 to 2014, with resected benign or borderline PTs. Information on age, size of primary tumor and recurrence, histo-
288
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
V. S. Klimberg, MD
References 1. Tummel E, Ochoa D, Korourian S, et al. Does axillary reverse mapping prevent lymphedema after lymphadenectomy? Ann Surg. 2016; http://dx.doi.org/10.1097/SLA. 0000000000001778. 2. Yue T, Zhuang D, Zhou P, et al. A prospective study to assess the feasibility of axillary reverse mapping and evaluate its effect on preventing lymphedema in breast cancer patients. Clin Breast Cancer. 2015; 15:301-306.
Given the rarity of the disease and conflicting surgical recommendations from various publications, PTs of the breast are challenging. As noted in this article by Borhani-Khomani and colleagues, the Danish Breast Cancer Cooperative Group recommends wide local excision, defined as a resection margin of greater than 1 cm, for all histological types of PTs. Wide excision is also recommended by the National Comprehensive Cancer Network.1 This study does not appear to clarify the margin extent required to reduce local recurrence. This was a retrospective study of 479 cases with a reported local recurrence rate of 6.3%
Clinical feasibility of Axillary Reverse Mapping and its influence on breast cancer related lymphedema: a systematic review
Experience in 871 patients, 19791993. Ann Surg. 1997;225:370-376. 6. McLaughlin SA, Stempel M, Morris EA, Liberman L, King TA. Can magnetic resonance imaging be
Eur J Obstet Gynecol Reprod Biol 200:117-122, 2016
until May 13, 2015. The level of evidence of these studies was low (mostly level 3). Therefore the conclusions are that the ARM procedure is feasible although ARM-node rates have a broad range. Additionally, from a theoretical point there is a clear benefit from ARM in terms of lymphedema prevention. From a practical point there is little scientific data to support this due to the lack of studies; and especially because of the different methods and definitions for lymphedema used in the different studies.
Breast cancer is the most common malignancy in women worldwide. Fortunately, the overall survival is good. Therefore it is important to focus on the morbidities related to breast cancer treatment. One of the most dreaded morbidities is lymphedema. In 2007 the Axillary Reverse Mapping (ARM) was introduced to limit the invasiveness in the axilla during breast cancer surgery. It is hypothesized that ARM is able to limit the incidence of breast cancer related lymphedema (BCRL) considerably. This systematic review aims to answer the following research questions: (1) which approaches for ARM are described? (2) Is ARM surgical feasible and oncological safe? (3) Does ARM decrease the incidence of lymphedema after sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND)? In total 27 papers were retrieved using four electronic databases (PubMed, Web of Science, Medline and Cochrane clinical trials; assessed
As one can see from this welldone and thorough systematic review by Gebruers and Tjalma, the incidence of BCRL varies widely depending on the surgery performed, who is performing it, the measurement technique, and the timing. The fact that surgeons doing supposedly the same operation, whether it is an SLNB or ALND, have lymphedema rates from 0% to 13% and 7% to 77%, respectively, gives rise to the hope that refining our technique may help prevent lymphedema. As practiced around the world, the technique of ALND, and even SLNB, is not standardized, compromising the staging of and recurrence in the axilla as well as the risk of lymphedema. Some may surmise that the risk of lymphedema with SLNB is low already, but remember that most lymphedema after an SLNB occurs from a negative SLNB, which ultimately has no benefit to the patient. In reality, today, just as many women per 100 who undergo an
Gebruers N, Tjalma WAA (Dept of Rehabilitation Sciences and Physiotherapy, Wilrijk, Belgium; Faculty of Medicine and Health Sciences, Wilrijk, Belgium; et al)
used to select patients for sentinel lymph node biopsy in prophylactic mastectomy? Cancer. 2008;112: 1214-1221.
axillary surgery develop lymphedema from an SLNB as from an ALND. This is true in that although the rate of BCRL is lower in SLNB than in ALND, many more women will undergo an SLNB for breast cancer staging. In addition, the burden of lymphedema from the patient’s perspective is quite significant, with many patients fearing BCRL more than a mastectomy. In summary, we need a better surgery. When Fo¨ldi first described the lymphatic drainage of the upper extremity, he carefully detailed which part of the arm drained in which direction, with the bulk of the drainage coalescing in the upper volar surface of the arm, from which it then drained into the axilla. However, once in the axilla, he did not delineate the drainage further, just labeling axillary lymph nodes as such. In fact, when in the axilla, nodes appear the same whether draining the breast, the back, or the upper extremity. Our group has hypothesized that BCRL developed in large part from surgical disruption of the lymphatics.1 Therefore, split mapping of the arm and the breast could delineate which lymph nodes should be taken and which should be spared. We first described the feasibility of this approach, coined the term ARM, and described the variations of ARM lymphatics, some of which draped very low in the axilla. Unfortunately, most who have tried to substantiate our work as detailed in this article have not used split mapping, as we first specified for the ARM
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
287
procedure, but only lymphangiography of the upper extremity.1 As we first reported, there is at least 4% crossover, such that it is important to know when this happens, for then the ARM node is the sentinel lymph node, and we would expect a high rate of positivity when ARM is performed on all comers. When this crossover happens, then the ARM nodes should be resected as a sentinel lymph node. We have looked at how often the ARM node is positive when there is not crossover with the breast lymphatics; it is not often, and it has been reported only when N2 disease is present, in which case these patients would receive radiation. We have recently reported our prospective phase II cumulative experience in 654
patients.1 Our lymphedema rate was less than 1% for SLNB and 6% for ALND. Yue and colleagues2 reported the only small randomized trial in ALND patients that shows a similar BCRL rate of 6% with ARM versus 33% without ARM.2 In the last several years, we have been dissecting the afferent and efferent lymphatics of any nodes to be removed and have reanastomosed/re-approximated lymphatics, and, with a short follow-up, we reported no lymphedema in 81 patients.1 ARM is a feasible procedure when done properly. We long ago proposed and are now shepherding a large prospective randomized protocol through the cooperative group mech-
anism that will help determine the safety and efficacy of this technique.
Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors: A Danish Population-Based Retrospective Study
logical grade, surgical treatment, margin size, and local recurrence were collected from the national Danish Pathology Register. Results.dA total of 479 cases were identified; 354 benign (74%), 89 borderline (19%), 6 uncertain histological grading (1.2%), and 30 possibly PT (6%). The mean age at presentation was 45.6 years (range 18e85), the mean tumor size was 3.5 cm (range 0.5e21), and the mean follow-up time was 98 months (range 1.1e192). We identified 30 local recurrences, i.e., a recurrence rate of 6.3%. Twenty-three recurrences had similar or lower histological grading than the primary tumor, one primary benign PT recurred as a tumor with unclear diagnosis, and one primary borderline PT recurred as malignant. The number of recurrences was too low, and the information on the size of the closest resection margin was too sparse to estimate an adequate margin size for excision of nonmalignant PTs.
Conclusions.dThe recurrence rate of PTs was considerably lower than previously stated in literature. No apparent pattern of progression in histological grading was found. The results do not justify wide excision margins of nonmalignant phyllodes tumors of the breast.
Borhani-Khomani K, Talman M-LM, Kroman N, et al (Univ of Copenhagen, København N, Denmark; Copenhagen Univ Hosp, København Ø, Denmark) Ann Surg Oncol 23:1543-1548, 2016
Purpose.dTo determine the recurrence rate of benign and borderline phyllodes tumors (PTs) of the breast, the association between the size of resection margin and risk of recurrence and the risk of progression of histological grading at recurrence. Methods.dNationwide retrospective study on Danish women aged 18 years or older, operated from 1999 to 2014, with resected benign or borderline PTs. Information on age, size of primary tumor and recurrence, histo-
288
Breast Diseases: A Year BookÒ Quarterly Vol 27 No 4 2017
V. S. Klimberg, MD
References 1. Tummel E, Ochoa D, Korourian S, et al. Does axillary reverse mapping prevent lymphedema after lymphadenectomy? Ann Surg. 2016; http://dx.doi.org/10.1097/SLA. 0000000000001778. 2. Yue T, Zhuang D, Zhou P, et al. A prospective study to assess the feasibility of axillary reverse mapping and evaluate its effect on preventing lymphedema in breast cancer patients. Clin Breast Cancer. 2015; 15:301-306.
Given the rarity of the disease and conflicting surgical recommendations from various publications, PTs of the breast are challenging. As noted in this article by Borhani-Khomani and colleagues, the Danish Breast Cancer Cooperative Group recommends wide local excision, defined as a resection margin of greater than 1 cm, for all histological types of PTs. Wide excision is also recommended by the National Comprehensive Cancer Network.1 This study does not appear to clarify the margin extent required to reduce local recurrence. This was a retrospective study of 479 cases with a reported local recurrence rate of 6.3%