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Axillary reverse mapping (ARM): Initial results of phase II trial in preventing lymphedema after lymphadenectomy
Abstract
Axillary reverse mapping (ARM) is unproven in preventing lymphedema. The purpose of this study is to evaluate lymphedema rates with ARM added to lymphadenectomy.
In this IRB approved study, 156 cases of SLNB/ALND from May 2007 to March 2010 were prospectively accrued to the study. Patients with an increase in arm volume greater than 20% over the contralateral side were considered to have lymphedema. Data was collected on identification and variations in lymphatic drainage, nodal status, ARM lymphatics preservation rate, adjuvant treatment (XRT, chemo) and lymphedema rate.
114 patients underwent SLNB only and 42 patients underwent ALND after SLNB, with a SLN identification rate of 100%. Median age was 56.9(±12.5) and BMI was 29.4(±6.9). Mean follow up was 14.6±9.4 months. ARM lymphatics were near or in the SLN field in 45/114 (39%) of the SLNB cases and in 34/42 (81%) of the ALND. ARM nodes were preserved in 92.3% of the cases (144/156). A total of 12 ARM nodes were resected because of crossover or suspicious appearance. The 2 ARM nodes involved by malignancy were in heavily positive axilla (>5 positive nodes). Lymphedema was diagnosed in 3.5% (4/114) of the SLNB cases and 7%(3/42) of the combined SLNB+ALND cases. 2.9% (4/140) of the patients who had the ARM lymphatics preserved and 18.7%(3/16) who had it transected developed clinical lymphedema. No regional recurrences were seen.
Preserving the ARM nodes is safe and resulted in a low incidence of postoperative lymphedema after SLNB and ALND.
... Besides, different volumes of blue dye were used, ranging from 1 to 5 mL. Six studies used 2-5 mL blue dye [12,26,[30][31][32][33] compared to the 1 mL of blue dye that was used in two other studies [21,27]. The visualisation rates of the studies using 2-5 mL blue dye were much higher than the visualisation rates reported by Ponzone et al. and Kuusk et al. who used only 1 mL (Table 2). ...
... In the same study, visualisation of the ARM lymph nodes and the ARM lymphatics during SLNB was only 43 and 19 %, respectively. In a subsequent larger study published in 2012, Noguchi et al. achieved an Table 2 Results of axillary reverse mapping procedure (3) Bedrosian et al. [23] 30 ( (14) Han et al. [17] 148 (156) 47/156 (30) 34/42 (L) (81) 2/12 (17) 45/114 (L) (39) 8/156 (5) Boneti et al. [30] 97 (97) 0/97 (0) NA 2/17 (12) NA 7/97 (7) Connor et al. [25] 184 ( (4) Beek et al. [43] 112 ( patients with a radiological complete or partial response of the axillary lymph nodes on ultrasound scans after NAC; USG-patients with a radiological stable or progressive disease of the axillary lymph nodes on ultrasound scans after NAC; NA not applicable identification rate of 85 % of ARM lymph nodes in the ALND field [38]. However, lower identification rates were reported during SLNB due to the fact that ARM lymph nodes are anatomically located at a higher level in the axilla than the SLN similar when using a blue dye [39]. ...
... Ten studies reported on the incidence of upper extremity lymphedema in patients who underwent ALND with or without preserving the ARM lymph nodes and/or lymphatics ( Table 3). The incidence of upper extremity lymphedema was evaluated by different measurement methods: four studies used water displacement to evaluate the incidence of upper extremity lymphedema Table 3 The [1,20,30,32], five studies measured the arm circumference and one study used a questionnaire survey [17-19, 35, 39, 47] (Table 3). ...
Axillary reverse mapping (ARM) is a technique by which the lymphatic drainage of the upper extremity that traverses the axillary region can be differentiated from the lymphatic drainage of the breast during axillary lymph node dissection (ALND). Adding this procedure to ALND may reduce upper extremity lymphedema by preserving upper extremity drainage. This review of the current literature on the ARM procedure discusses the feasibility, safety and relevance of this technique. A PubMed literature search was performed until 12 August 2015. A total of 31 studies were included in this review. The studies indicated that the ARM procedure adequately identifies the upper extremity lymph nodes and lymphatics in the axillary basin using blue dye or fluorescence. Preservation of ARM lymph nodes and corresponding lymphatics was proven to be oncologically safe in clinically node-negative breast cancer patients with metastatic lymph node involvement in the sentinel lymph node (SLN) who are advised to undergo a completion ALND. The ARM procedure is technically feasible with a high visualisation rate using blue dye or fluorescence. ALND combined with ARM can be regarded as a promising surgical refinement in order to reduce the incidence of upper extremity lymphedema in selected groups of patients.
... Three different procedures were described to perform the ARM. First, multiple authors described the use of a blue dye [13,[15][16][17][18][19][21][22][23][24][25][28][29][30]32,34,35,39] that was injected dermally or subcutaneous; mostly on the upper inner arm or hand, on the ipsilateral side. Overall, 2-5 ml of blue dye was injected; the injection point was massaged for 5 min or more and the injection was done 15-60 min before SLNB and/or ALND. ...
... Boneti [18] ALND/SLNB Not mentioned 1.8% (2/131) Not mentioned Boneti [17] ALND/SLNB Water displacement/!20% difference 3.9% (2/51 6 months Thompson [13] ALND/SLNB Not mentioned 2.5% 51/40) 8 months Boneti [19] ALND Water displacement/!20% difference 7% (3/42) 14.6 AE 9.4 (6-36) months Casabona [29] ALND Lymphangioscintigraphy 0% (0/9) 9 months Gennaro [20] ALND patients. The incidences ranged from 0 to 30.7% and 0 to 4% in ALND and SLN-samples treated with ARM. ...
... A different definition has a large impact on the incidences found as clearly presented in the studies of Armer et al. [46,47] Since the >10% volume difference is the most common used definition to diagnose lymphedema, it is clear that using a definition of >20% difference will generate a lower incidence. In the studies concerning ARM, we have found that three studies [17,19,34] used the >20% difference definition and these results need to be interpreted with caution (see Table 2). Therefore it is important to compare studies that have used the same assessment and definition. ...
... Eleven studies performed ARM procedures during SLNB [5,9,11,27,28,[30][31][32][37][38][39], and 20 studies performed ARM procedures during ALND [6-8, 11, 25, 26, 28-38, 40-42]. All studies were prospectively designed, with 23 singly-arm studies performing ARM during SLNB or ALND, and only 1 randomized controlled trial comparing the outcomes between ARM patients and non-ARM patients [42]. ...
... With respect to ARM mapping materials, 17 studies used blue dye alone [5-7, 9, 11, 25-30, 32, 36-38, 40, 41]; 2 studies used fluorescence alone [31,35]; 1 study used blue dye in combination with fluorescence [39]; 3 studies used blue dye together with radioisotope [8,34,42]; and 1 study used radioisotope [33]. Seven studies were from North America [5,7,11,26,28,37,38], nine from Europe [6,8,9,25,29,[32][33][34]41], seven from Asia [27,30,31,35,36,39,42], and 1 from the South America [40]. The characteristics of included studies were shown in Table 1. ...
... Eleven studies reported data on outcomes of ARM procedures during SLNB [5,9,11,27,28,[30][31][32][37][38][39]. The identification rate of ARM nodes or lymphatics was reported by 8 studies [5,9,11,28,31,[37][38][39]. ...
Objective:
The axillary reverse mapping (ARM) technique has recently been developed to prevent lymphedema by preserving the arm lymphatic drainage during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) procedures. The objective of this systematic review and meta-analysis was to evaluate the feasibility and oncological safety of ARM.
Methods:
We searched Medline, Embase, Web of science, Scopus, and the Cochrane Library for relevant prospective studies. The identification rate of ARM nodes, the crossover rate of SLN-ARM nodes, the proportion of metastatic ARM nodes, and the incidence of complications were pooled into meta-analyses by the random-effects model.
Results:
A total of 24 prospective studies were included into meta-analyses, of which 11 studies reported ARM during SLNB, and 18 studies reported ARM during SLNB. The overall identification rate of ARM nodes was 38.2% (95% CI 32.9%-43.8%) during SLNB and 82.8% (78.0%-86.6%) during ALND, respectively. The crossover rate of SLN-ARM nodes was 19.6% (95% CI 14.4%-26.1%). The metastatic rate of ARM nodes was 16.9% (95% CI 14.2%-20.1%). The pooled incidence of lymphedema was 4.1% (95% CI 2.9-5.9%) for patients undergoing ARM procedure.
Conclusions:
The ARM procedure was feasible during ALND. Nevertheless, it was restricted by low identification rate of ARM nodes during SLNB. ARM was beneficial for preventing lymphedema. However, this technique should be performed with caution given the possibility of crossover SLN-ARM nodes and metastatic ARM nodes. ARM appeared to be unsuitable for patients with clinically positive breast cancer due to oncological safety concern.
... Besides, different volumes of blue dye were used, ranging from 1 to 5 mL. Six studies used 2-5 mL blue dye [12,26,[30][31][32][33] compared to the 1 mL of blue dye that was used in two other studies [21,27]. The visualisation rates of the studies using 2-5 mL blue dye were much higher than the visualisation rates reported by Ponzone et al. and Kuusk et al. who used only 1 mL (Table 2). ...
... Ten studies reported on the incidence of upper extremity lymphedema in patients who underwent ALND with or without preserving the ARM lymph nodes and/or lymphatics ( Table 3). The incidence of upper extremity lymphedema was evaluated by different measurement methods: four studies used water displacement to evaluate the incidence of upper extremity lymphedema [1,20,30,32], five studies measured the arm circumference and one study used a questionnaire survey [17-19, 35, 39, 47] (Table 3). ...
Any surgical intervention in the axilla may potentially result in lymphoedema of the upper extremity. The concordance of the sentinel nodes draining the upper extremity and sentinel nodes draining the breast is the probable cause of lymphoedema after SLN biopsy in breast cancer. Axillary reverse mapping (ARM) is a feasible technique that may reduce lymphoedema rates in breast cancer patients while preserving the oncological safety of the procedure. Preservation of axillary reverse mapping nodes results in a low incidence of lymphoedema during sentinel node biopsy and axillary node dissection. The potential benefit of the ARM technique needs to be evaluated in a controlled randomized trial to confirm the findings of the reported institutional protocols.
... This is an extension of our ongoing series and 4th publication on this cohort which began in May 2006. 35 ...
... 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. 34,35,38 Also 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, one from the breast and one from the arm determines the presence of crossover between the breast and arm drainage. ...
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.
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.
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).
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.
Copyright © 2014. Published by Elsevier Inc.
... A large phase 2, single-arm trial with 654 patients evaluated the feasibility of ARM. They reported the identification of blue UE lymphatics in 29% of SLNB patients and 72% of ALND patients (90)(91)(92)(93)(94)(95)(96)(97)(98) patients combined. They found the feasibility to be 37% in SLNB and 82% in ALND (99). ...
Background
Breast cancer- related lymphedema (BCRL) affects about 3 to 5 million patients worldwide, with about 20,000 per year in the United States. As breast cancer mortality is declining due to improved diagnostics and treatments, the long-term effects of treatment for BCRL need to be addressed.
Methods
The American Society of Breast Surgeons Lymphatic Surgery Working Group conducted a large review of the literature in order to develop guidelines on BCRL prevention and treatment. This was a comprehensive but not systematic review of the literature. This was inclusive of recent randomized controlled trials, meta-analyses, and reviews evaluating the prevention and treatment of BCRL. There were 25 randomized clinical trials, 13 systemic reviews and meta-analyses, and 87 observational studies included.
Results
The findings of our review are detailed in the paper, with each guideline being analyzed with the most recent data that the group found evidence of to suggest these recommendations.
Conclusions
Prevention and treatment of BCRL involve a multidisciplinary team. Early detection, before clinically apparent, is crucial to prevent irreversible lymphedema. Awareness of risk factors and appropriate practice adjustments to reduce the risk aids are crucial to decrease the progression of lymphedema. The treatment can be costly, time- consuming, and not always effective, and therefore, the overall goal should be prevention.
... [18] Boneti et al. also reported that among 114 patients who underwent ARM, lymphedema was diagnosed in 3.5% of the SLNB cases and 7% of the combined SLNB + ALND cases. [19] The results of our study were somehow in line with these reports. As mentioned above, we found that 10% of our cases developed lymphedema after the procedures that are relatively higher than previous reports. ...
Background: The axillary reverse mapping (ARM) technique identifies and preserves arm nodes
during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Here, we aimed
to investigate the prevalence of lymphedema following ARM. Materials and Methods: This is a
clinical trial that was performed in 2019‑2020 in Isfahan on patients with breast cancer in the early
stages. Demographic and initial information of all cases including age and body mass index (BMI)
was collected. Patients were then underwent SLNB ± ALND associated with ARM and were
followed up for lymphedema every 6 months to a year. The occurrence of lymphedema was assessed.
Results: By evaluating data of 102 patients, we found that 10 patients (9.8%) had lymphedema
and patients with lymphedema had significantly higher age (P = 0.004), higher BMI (P = 0.001),
larger tumor size (P = 0.018), and longer surgery duration (P < 0.001). The frequency of
menopausal women was higher in patients with lymphedema compared to other cases (P = 0.001).
Conclusion: The prevalence of lymphedema was high among patients undergoing ARM that was
associated with factors including higher age, higher BMI, prolonged surgery duration, larger tumor
size, and menopause. We believe that further comparative studies should be conducted on this issue.
... Strategies to prevent arm lymphedema development have focused mainly on the modification of surgical practices and cancer treatment regimens with positive results (2,(14)(15)(16). However, one of the primary goals of cancer treatment is preventing cancer recurrence, and whether changes to cancer treatment necessary to reduce the risk of lymphedema negatively affect cancer recurrence rates long-term remains to be determined (16,17). This highlights the importance of identifying modifiable risk factors that are distinct from cancer treatment that may contribute to lymphedema development. ...
Background:
To assess the risk of lymphedema associated with the use of calcium channel blockers (CCB) among breast cancer patients.
Methods:
A nested case-control study of adult female breast cancer patients receiving an antihypertensive agent was conducted using administrative claims data between 2007 and 2015. Cases were patients with lymphedema who were matched to 5 controls based on nest entry date (±180 days), age (±5 years), number of hypertensive drug classes, Charlson Comorbidity Index (CCI), thiazide exposure, and insurance type. Exposure to CCBs and covariates was identified in the 180-day period prior to event date. Conditional logistic regression was used to assess the impact of exposure among cases and controls.
Results:
A total of 717 cases and 1,681 matched controls were identified. After matching on baseline characteristics, mastectomy (7.8% vs. 4.8%; P = 0.0039), exposure to radiotherapy (27.1% vs. 21.7%; P = 0.0046), taxane-based chemotherapy (11.7% vs. 7.4%; P = 0.0007), anthracycline-based chemotherapy (6.0% vs. 3.6%; P = 0.0073), CCB use (28.3% vs. 23.3%; P = 0.0087), and CCI (19.8% vs. 12.7%; P < 0.0001; score of 4 or above) were all higher in cases during the 180 days prior to the event date. In the adjusted analysis, CCB exposure was significantly associated with increased risk of lymphedema (OR = 1.320; 95% confidence interval, 1.003-1.737).
Conclusions:
CCB use was significantly associated with the development of lymphedema in breast cancer patients.
Impact:
CCBs should be avoided or used with caution in breast cancer patients to reduce the risk for developing lymphedema.
... These types of products worn on the limb during the day are a safe and effective 52 . The SNB procedure, on the other hand, does not cause significant risks because it induces low incidence of this complication 53 . After removing the sutures and healing of the wound, the patient can start out-patient physical therapy. ...
Introduction: Breast cancer is the most common malignant tumour and the second cause of death among women in Poland following lung cancer. Its therapy includes a number of procedures, including surgical treatment, the choice of which depends, among others, on the histological form of the cancer and disease severity. In recent years, radical surgical techniques have been replaced by conserving ones, and in the context of routine resection of the axillary lymph nodes (lymphadenectomy), biopsy was introduced, i.e. sentinel lymph node biopsy (SNB). Also, wide access to reconstructive treatments carried out with various techniques, using patients’ own tissues or artificial materials (breast implants) have been applied.
Study aim: The aim of the work is to present the current state of knowledge on the principles of breast cancer treatment and its undesirable consequences, as well as the selection of physiotherapeutic methods depending on the type of upper limb dysfunction as a result of the performed surgery.
Research materials: The research materials consist of patients treated using various surgical and oncological methods as well as physiotherapeutic procedures at the Holy Cross Oncology Centre in Kielce, from 2014 to 2016. The written consent of the Clinic Chief and patients for the publication of their image was obtained. The authors of the work do not indicate any conflict of interest.
Research Methods: The research methodology was based on the presentation of selected patients treated using various oncological and surgical methods for breast cancer treatment, as well as characterization of the physiotherapeutic methods necessary in restoring expected functional upper limb status in these patients.
Conclusions: Modern methods used in breast cancer treatment should be conditioned by good cooperation of an entire team of specialists from various clinical areas and physiotherapists. The purpose of this procedure is to cure the patient, minimize the occurrence of complications and adverse side effects, and restore functional capacity. An integral part of such breast cancer treatment patients is, among others, their effective rehabilitation.
... Patients with known breast cancer underwent intraoperative injection of unfiltered technectium 99 sulfur colloid in the subareolar plexus of the breast and lymphazurin blue in the upper inner volar surface of the arm for sentinel lymph node biopsy and axillary reverse mapping. 12 All patients underwent total skin sparing mastectomy (nipple skin sparing mastectomy) via a vertical incision from the limbus to the inframammary fold. 13 Pectoralis fascia was taken in all patients. ...
Background:
Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support.
Methods:
In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal.
Results:
Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R(2) = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery.
Conclusions:
The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after major surgery in patients with non-cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non-cachectic early stage breast cancer after major surgery.
... This is extremely important for patients at risk of lymphoedema, i.e. after armpit lymphadenectomy. The SLNB procedure does not pose a significant risk of the emergence of this complication, because it is only recognised in 3-7% of women after the surgery [27,28]. ...
In recent years, radical surgical techniques have been replaced with conserving ones, and a sentinel lymph node biopsy was introduced in the case of routine lymphadenectomy. Subcutaneous amputation with an immediate breast reconstruction or radical breast amputation in Madden modification are used in advanced tumours. Breast conserving surgery and effective neoadjuvant therapy reduce the range of the operation and postoperative complications. Similarly, breast reconstructions do not increase the risk of cancer development, and they do not impede the detection of a local recurrence. This paper presents the most commonly used types of surgery used to treat breast cancer, and the possibility of a surgical reconstruction of the breast. The methods of physiotherapeutic management in particular stages of treating women both after radical surgeries and reconstructions, including the aspect of maintaining their physical activity and mental balance are discussed.
... Several studies have shown that the use of ARM and selective axillary dissection can significantly reduce the incidence of lymphoedema after breast surgery and also patient perceived lymphoedema (26)(27)(28)(29) however the literature in not unanimous and some studies found it had no benefit in reducing lymphoedema (30). ...
Early detection and diagnosis of upper extremity lymphoedema in patients after mastectomy and axillary lymph node clearance is important in order to treat disease before it is too advanced to achieve favourable outcomes. Patients with disease refractory to conservative management can be efficiently assessed for diagnosis and surgical intervention using advanced lymphatic imaging techniques. The current paper highlights the more readily available of these: lymphoscintigraphy, indocyanine green (ICG) lymphangiography and immunofluorescence, magnetic resonance lymphangiography (MRL) and computed tomographic lymphangiography in combination or individually. With such techniques, both diagnosis and treatment of lymphoedema has become more readily achieved, with lymphatico-venous and lymphatico-lymphatic anastomosis, and lymph node transfer now increasingly common undertakings.
... This phenomenon is seen in clinical studies in which crossover of SLNB/ALND and ARM-nodes are reported, rightfully raising doubts on the oncological safety of the ARM technique [33]. Moreover, the efficacy of sparing ARMnodes for reducing the incidence of BCRL has yet to be confirmed in long-term follow-up studies [34,35]. ...
Primary aim is to give an overview of changes in axillary staging and treatment of breast cancer patients. Secondly, we aim to identify patients with a high arm/shoulder morbidity risk, and describe a strategy to improve early detection and treatment. Recent and initiated studies on axillary staging and treatment were evaluated and clustered for clinically node negative and clinically node positive breast cancer patients, together with studies on pathology, detection and (surgical) prevention and treatment of lymphedema. For clinically node negative patients, the indication for axillary lymph node dissection in sentinel node positive patients is fading. On the contrary, clinically node positive patients are routinely subjected to an axillary lymph node dissection, in combination with other therapies associated with an increased lymphedema risk, such as mastectomy, adjuvant radiation- and (taxane-based) chemotherapy. Techniques for prevention, early detection and (surgical) treatment of lymphedema are being developed. Axillary staging and treatment in breast cancer patients with a clinically node negative status will become less invasive, thereby reducing the incidence of morbidity. Nevertheless, in patients with a clinically node positive status, aggressive treatment will still be required for oncologic control. For these patients, a surveillance program should be implemented in order to apply (curative) surgical treatment for lymphedema.
Copyright © 2015 Elsevier Ltd. All rights reserved.
... New emerging treatments were under investigation, including aquatherapy (Johansson et al., 2013;Tidhar & Katz-Leurer, 2010), axillary reverse mapping (Boneti et al., 2012), cell transplantation (Maldonado et al., 2011), massage (Maher, Refshauge, Ward, Paterson, & Kilbreath, 2012), qigong (Fong et al., 2014), the use of a device delivering electronic sound waves and vacuum (Cavezzi, Paccasassi, & Elio, 2013), extracorporeal shockwave therapy (Bae & Kim, 2013), use of a mechanical exercise device (Bordin, Guerreiro Godoy, & Pereira de Godoy, 2009;Guerreiro Godoy, Guimaraes, Oliani, & Pereira de Godoy, 2011;Guerreiro Godoy, Oliani, & Pereira de Godoy, 2010;Guerreiro Godoy, Pereira, Oliani, & Pereira de Godoy, 2012), low-intensity electrostatic stimulation (Belmonte et al., 2012), and lumbar sympathetic ganglion block (Woo, Park, Kim, & Kim, 2013). ...
Cancer-related lymphedema is a progressive and chronic syndrome of abnormal swelling and multiple symptoms resulting from cancer treatment. Even with modern medical advances, lymphedema remains a major health problem affecting thousands of cancer survivors. To provide healthcare professionals with evidence-based clinical practice guidelines for lymphedema treatment and management, a systematic review was conducted to evaluate 75 selected articles from 2009-2014 by the Oncology Nursing Society Putting Evidence Into Practice lymphedema team. Findings of the systematic review support complete decongestive therapy, compression bandages, and compression garments with highest evidence for best clinical practice. Weight management, full-body exercise, information provision, prevention, and early intervention protocols are likely to be effective for clinical practice. Historic recommendations for activity restriction and avoidance of aerobic and resistive exercises that limit cancer survivors' daily lives have been challenged with more evidence. Cancer survivors may not need to restrict activities such as resistive or aerobic exercises and weightlifting with gradual exercise progression. Future research should focus on providing high-level evidence using randomized clinical trials with larger samples and studying lymphedema beyond breast cancer.
... These issues may represent an important drawback for the implementation of the ARM procedure. Boneti et al. recently published a phase II trial of ARM with promising results [16]. The study showed that preserving the ARM nodes in a clinically negative axilla is safe, and results in a low incidence of postoperative lymphedema in patients undergoing ALND and SLNB. ...
Axillary lymph node dissection (ALND) in patients with breast cancer has the potential to induce side-effects, including upper-limb lymphedema. Axillary reverse mapping (ARM) is a technique that enables discrimination of the lymphatic drainage of the breast from that of the upper limb in the axillary lymph node (LN) basin. If lymphedema is caused by removing these lymphatics and nodes in the upper limb, the possibility of identifying these lymphatics would enable surgeons to preserve them. The aim of this study is to determine the clinical relevance of selective axillary LN and lymphatic preservation by means of ARM. To minimize the risk of overlooking tumor-positive ARM nodes and the associated risk of undertreatment, we will only include patients with a tumor-positive sentinel lymph node (SLN). Patients who are candidates for ALND because of a proven positive axillary LN at clinical examination can be included in a registration study.
The study will enroll 280 patients diagnosed with SLN biopsy-proven metastasis of invasive breast cancer with an indication for a completion ALND. Patients will be randomized to undergo standard ALND or an ALND in which the ARM nodes and their corresponding lymphatics will be left in situ. Primary outcome is the presence of axillary surgery-related lymphedema at 6, 12, and 24 months post-operatively, measured by the water-displacement method. Secondary outcome measures include pain, paresthesia, numbness, and loss of shoulder mobility, quality of life, and axillary recurrence risk.
The benefit of ALND in patients with a positive SLN is a subject of debate. For many patients, an ALND will remain the treatment of choice. This multicenter randomized trial will provide evidence of whether or not axillary LN preservation by means of ARM decreases the side-effects of an ALND. Enrolment of patients will start in April 2013 in five breast-cancer centers in the Netherlands, and is expected to conclude by April 2016.
Trial registration
TC3698
Objective:
Secondary lymphoedema (LE) is a chronic condition with limited surgical treatment options for restoring extremity form and function. This study aims to establish a reproducible model of secondary LE and evaluate the preventive and corrective effects of fenestrated catheters (FC) and capillary tubes (CT).
Methods:
A total of 35 rats underwent left hindlimb inguinal and popliteal node dissection, followed by radiotherapy after two weeks. The right hindlimb served as the control. Rats were divided into five groups: sham, two preventive (Group 2 - EFC, Group 3 - ECT), and two corrective (Group 4 - LFC, Group 5 - LCT). Measurements of ankle circumference (AC) and paw thickness (PT) were taken weekly, and imaging modalities were performed. After a 16 week follow up, rats were euthanised for histological examination.
Results:
Data include paw thickness (PT) and ankle circumference (AC) ratios for hindlimbs. In the sham group, AC ratio was 1.08 (p = .002) and PT ratio was 1.11 (p = .020), confirming successful lymphoedema model establishment. Early catheter and tube placement in Groups 2 and 3 prevented AC and PT increase until the 16th week. Group 2: AC ratio was 0.98 (p = .93), PT ratio was 0.98 (p = .61). Group 3: AC ratio was 0.98 (p = .94) and PT ratio was 0.99 (p = .11). From the 10th to the 16th week, Groups 4 and 5 exhibited reduced measurements after insertion of catheters and tubes. Computed tomography imaging as an objective examination supported the results obtained from the measurements. The histological findings confirmed the benefits of both FC and CT.
Conclusion:
The insights gained from the present study provide a basis for further exploration and refinement of drainage system designs, ultimately leading to improved treatment approaches for individuals suffering from lymphoedema in the future.
Tremendous progress has been made over the past several decades in the treatment of breast cancer. Mortality and recurrence rates continue to decline. Our ability to tailor patient and tumor specific treatments have rapidly advanced. The vast majority of our patients can safely have breast conservation. Unfortunately for many patients, survivorship is burdened by ongoing quality of life issues. Most breast cancer patients are asymptomatic at presentation and the onus is on us to preserve this. Surgery, radiation and systemic therapy can result in long term toxicities which can be amplified with a multimodality approach. We must strive to apply minimally effective therapies rather than a maximally tolerated approach. Breast cancer related lymphedema (BCRL) is particularly dreaded chronic complication. This review will strive to give the reader a better understanding of BCRL and shed light on wisely choosing the integration of treatment modalities to minimize BCRL risk. Key literature as emerging concepts will be highlighted.
Breast development begins in the 5th and 6th weeks of fetal development and continues through puberty. Errors during development can lead to abnormal development or complete failure of breast development. The breast comprises several structures that are both functional and supportive. Some of these structures do not fully develop until pregnancy and lactation and regress or involute after lactation and at menopause. The anatomy of the breast and axilla is important in oncological surgery and must be considered during surgical planning to ensure the proper treatment of breast cancer.
The surgical approach of the axilla in patients with early-stage breast cancer has witnessed considerable evolution during the past 25 years. The previously undisputed gold standard of axillary-lymph-node dissection for staging has now been replaced by sentinel-lymph-node biopsy for patients with clinically negative axilla. For selected patients with limited sentinel-lymph-node involvement, completion axillary-lymph-node dissection can be omitted or replaced by axillary radiotherapy, reducing morbidity. The clinical interest of axillary staging after neoadjuvant chemotherapy is increasing and this approach might contribute to morbidity reduction, and to the further tailoring of future systemic and locoregional treatment decisions by response assessment. Refinement of the sentinel-lymph-node biopsy technique might overcome the slightly impaired success rates in this setting. New techniques for lymphatic mapping attempt to further simplify the procedure. In view of the declining influence of axillary nodal status on adjuvant therapy decision-making, ongoing clinical trials will evaluate whether sentinel-lymph-node biopsy can be avoided altogether in selected patients.
Our group has hypothesized that variations in the anatomical location of the arm lymphatic drainage system within the axilla put the arm lymphatics at risk for disruption during an SLNB and/or ALND. Therefore, mapping and protecting the drainage of the arm versus that of the breast within the axilla by split mapping using blue dye to identify and protect the lymphatics draining from the arm (axillary reverse mapping (ARM)) and radioactivity to map those draining from the breast would decrease the likelihood of inadvertent disruption during lymphadenectomy. Mapping and sparing the lymphatics draining the arm during SLNB or ALND decrease the subsequent development of lymphedema as compared to SLN mapping alone.
Breast development begins in the 5th and 6th weeks of fetal development and continues through puberty. Errors during development can lead to abnormal development or complete failure of breast development. The breast comprises several structures that are both functional and supportive. Some of these structures do not fully develop until pregnancy and lactation and regress or involute after lactation and at menopause. The anatomy of the breast and axilla are important in oncological surgery and must be considered during surgical planning to ensure the proper treatment of breast cancer.
Background:
Axillary reverse mapping (ARM) is a technique that discerns axillary lymphatic drainage of the arm from the breast. In the current study, we retrospectively evaluated the incidence of metastatic axillary lymph node involvement, including ARM lymph nodes, in clinically node positive breast cancer patients (cN+ patients) in whom neo-adjuvant chemotherapy (NAC) was administered followed by primary ALND using breast MRI.
Patients and methods:
Data from 98 cN+ breast cancer patients were analysed retrospectively. Patients without residual axillary disease at breast MRI following NAC (RAD-, n = 64) were compared with patients with residual axillary disease (RAD+, n = 34). Presence of suspect axillary lymph nodes on pre-NAC and post-NAC breast MRI was determined by experienced breast radiologists and was correlated to histopathological findings.
Results:
In the RAD-group residual axillary disease on pathological analysis following NAC was found in 25 patients (39.1%), as compared to 24 patients (70.6%) in the RAD + group (p = 0.003). Metastatic involvement of ARM lymph nodes following NAC was demonstrated in 5 patients (7.8%) in the RAD-group as compared to 10 patients (29.4%) in the RAD + group (p = 0.005).
Conclusion:
Breast MRI following NAC is not suitable to detect residual metastatic disease of the axilla. However, breast MRI post-NAC may be of use to identify cN+ patients with a low risk of ARM lymph node metastases. This may help to select a subgroup of cN+ patients in whom sparing of ARM lymph nodes during axillary lymph node dissection can be considered.
This paper focused on high-precision demodulation of wavelength shift of FBG sensor. Fiber tunable F-P filer was used as a demodulation method. 32-bit embedded processor ARM9-S3C2440 chip was used as the main controller and simulated annealing algorithm was realized on ARM to demodulate wavelength signal. Simulation results show that the simulated annealing algorithm is reliable to process analog signals on ARM chip and significant performance is achieved such as saving bandwidth, increasing the amounts of reusable fiber grating sensors in sensor system and speeding up data processing.
Cancer-related lymphedema is a progressive and chronic syndrome of abnormal swelling and multiple symptoms resulting from cancer treatment. Even with modern medical advances, lymphedema remains a major health problem affecting thousands of cancer survivors. To provide healthcare professionals with evidence-based clinical practice guidelines for lymphedema treatment and management, a systematic review was conducted to evaluate 75 selected articles from 2009–2014 by the Oncology Nursing Society Putting Evidence Into Practice lymphedema team. Findings of the systematic review support complete decongestive therapy, compression bandages, and compression garments with highest evidence for best clinical practice. Weight management, full-body exercise, information provision, prevention, and early intervention protocols are likely to be effective for clinical practice. Historic recommendations for activity restriction and avoidance of aerobic and resistive exercises that limit cancer survivors’ daily lives have been challenged with more evidence. Cancer survivors may not need to restrict activities such as resistive or aerobic exercises and weightlifting with gradual exercise progression. Future research should focus on providing high-level evidence using randomized clinical trials with larger samples and studying lymphedema beyond breast cancer.
The evidence available for risk reduction of lymphedema after breast cancer treatment is sparse and inconsistent. It is limited by confounding factors such as axillary disease burden, number of lymph nodes harvested, and radiation treatment. However, there are several strategies for prevention and risk reduction prior to the onset of lymphedema. Techniques such as sentinel lymph node biopsy, axillary reverse mapping, lymphatic anastomosis, and lymphovenular anastomosis are aimed at preventing or minimizing the disruption of lymphatic flow from the upper extremity. Few surgical procedures, such as the historical Charles procedure, as well as newer techniques including distal lymphaticovenular anastomosis, lymph node transfer, suction-assisted protein lipectomy, and low-level laser therapy exist. Nonsurgical treatments include complete decongestive therapy, pneumatic compression, Kinesio tape, and exercise. These have varying degrees of effectiveness but have limitations in patient compliance or availability of certified therapists.
Lymphedema of the arm after breast cancer treatment continues to challenge clinicians worldwide. In this review, we examine the main modalities, both nonsurgical and surgical, to prevent and treat this as yet incurable condition.
© 2015 Wiley Periodicals, Inc.
Axillary reverse mapping (ARM) is a technique to map and preserve upper extremity lymphatic drainage during axillary lymph node dissection (ALND) in breast cancer patients. We prospectively evaluated the metastatic involvement of ARM-nodes in patients who underwent an ALND for clinically node positive disease following (neo)adjuvant chemotherapy (NAC) in comparison to patients in whom primary ALND was performed without NAC.
Patients with clinically node positive invasive breast cancer, confirmed by fine needle aspiration cytology and scheduled for primary ALND were enrolled in the study. Patients were separated into two groups: one group treated with NAC (NAC+ group) and one group not treated with NAC (NAC- group). ARM was performed in all patients by injecting blue dye into the ipsilateral upper extremity. During ALND, ARM-nodes were first identified and removed separately, followed by a standard ALND.
91 patients were included in the NAC+ and 21 patients in the NAC- group. There was no difference in the ARM visualization rate between the two groups (86.8% for NAC+ group versus 90.5% for NAC- group, P = 0.647). In the NAC+ group 16.5% of the patients had metastatic involvement of the ARM-nodes versus 36.8% of the patients in the NAC- group (P = 0.048).
The risk of metastatic involvement of ARM-nodes in clinically node positive breast cancer patients is significantly lower in patients who have received NAC.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Recently, the American College of Surgeons Oncology Group Z0011 trial demonstrated that axillary lymph node dissection (ALND) could be safely avoided in selected breast cancer patients with limited nodal disease and having breast conservation therapy. However, for node positive (N+) mastectomy patients, full ALND remains the standard of care. Hypothesizing that omission of complete ALND is safe in many N+ breast cancer patients, a hybrid procedure called conservative axillary regional excision (CARE) was developed, consisting of removal of sentinel nodes and other palpable nodes (without intraoperative frozen section or reoperation for N+).
A retrospective review of patients undergoing mastectomy with CARE between 2002 and 2010 was performed. Data collected included demographics; staging; number of lymph nodes removed; adjuvant, antihormonal, and radiation therapies; recurrence; lymphedema; and survival data. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using Cox proportional hazards.
Five hundred and eighty-seven patients underwent mastectomy with CARE. Mean follow-up was 5.1 years. A median of 8 nodes were removed. There were 7 patients with local recurrence, of which 3 were axillary recurrences. Lymphedema developed in 20 (3.4%) patients, 75% of which had neoadjuvant chemotherapy. Lymphedema development was associated with the number of lymph nodes removed (p = 0.05) and radiation therapy (p = 0.004).
Conservative axillary regional excision is an excellent model for understanding the role of limited axillary surgery in mastectomy patients. The locoregional recurrence rate among N1 patients having CARE is low (3.4%). Conservative axillary regional excision is also associated with low rates of lymphedema. These data support the use of limited ALND in selected N+ mastectomy patients.
Excision followed by radiofrequency ablation (eRFA) is an intraoperative method that utilizes intracavitary hyperthermia to create an additional tumor-free zone around the lumpectomy cavity in breast cancer patients. We hypothesized that eRFA after lumpectomy for invasive breast cancer could reduce the need for re-excision for close margins as well as potentially maintain local control without the need for radiation.
Methods
This prospective Phase II institutional review board (IRB)-approved study was conducted from March 2004 to April 2010. A standard lumpectomy was performed, then the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 degrees C for 15 minutes. Validated doppler sonography was used to intraoperatively determine adequacy of ablation.
Results
100 patients were accrued to the trial with an average age of 65.02 years ± 10.0 years. The stages were Tis:30, T1mic:1, T1a:9, T1b:27, T1c:22, T2:10 T3:1. Grades were I: 48, II:29, III: 23. 78 subjects had margins >2 mm (negative), 22 patients had margins ≤ 2mm of which 12 were close and 3 focally positive which at our institution would have required re-excision (only one of this group had re-excision). There were 6% post-operative complications. 24 patients received XRT. During the study mean follow-up period of 62 months ± 24 months (68 month median follow-up) in patients not treated with XRT, there were 2 in site tumor recurrences treated with AI, 3 biopsy entrance site recurrences treated excision and XRT to conserve the breast, and 2 elsewhere recurrences and one contralateral recurrence all three treated with mastectomy.
Conclusions
Long-term follow-up suggests that eRFA may reduce the need for re-excision for close or focally positive margins in breast cancer patients. eRFA may be a valuable tool for treating favorable patients that desire lumpectomy who either cannot or do not want radiation. A multicenter trial has been initiated based on these results.
Objective
To analyze differences in lymphorrhea volume, the duration of axillary drainage, and length of hospital stay in patients who underwent axillary dissection with the harmonic scalpel (Focus®) and a sheet of collagen, fibrinogen and thrombin (TachoSil®) versus conventional lymphadenectomy with monopolar electrocautery.
Patients and methods
We performed a prospective randomized study in a hospital-based cohort from 2008 to 2011. Seventy-seven patients were randomized to lymphadenectomy using traditional surgery (control group) versus the harmonic scalpel and TachoSil® sheet. Length of hospital stay and axillary drainage volume and duration were compared between the 2 groups. The variables collected included the type and size of the tumor, the number of lymph nodes removed and involved, the level of lymphadenectomy, type of surgery, and age.
Results
There were 37 patients in the group that underwent lymphadenectomy with the harmonic scalpel and collagen sheet and 40 in the control group who underwent conventional lymphadenectomy with electrocautery. Compared with the control group, the harmonic scalpel and collagen sheet group showed reductions in the mean length of hospital stay (6.1 versus 4.25 days), the duration of lymphorrhea (9.5 versus 6.3 days), and the total volume (550 versus 330 cc); all these differences were statistically significant.
Conclusions
Axillary dissection with the harmonic scalpel and a single sheet of collagen and thrombin decreases length of hospital stay, the days necessary to remove the axillary drainage, and lymphorrhea volume.
A considerable percentage of breast cancer patients who have undergone an axillary lymph node dissection (ALND) experience postoperative complications, with lymphoedema occurring most frequently. Axillary Reverse Mapping (ARM) is a new technique in which the lymphatic drainage system of the upper extremity can be visualized during an ALND. If lymphoedema is caused by severing of the lymphatic drainage system or removal of its associated lymph nodes, the preservation of these structures should reduce the incidence of lymphoedema. Patients who might benefit from ARM are patients for whom a subsequent ALND is indicated following a positive sentinel lymph node diagnostic procedure, and perhaps also patients who have an indication for a primary ALND following neo-adjuvant chemotherapy. A multicenter RCT is to start in the near future, during which we will investigate whether the preservation of axillary lymph nodes results in reduced morbidity.
Axillary reverse mapping (ARM) is a novel technique to preserve upper extremity lymphatics that may reduce the incidence of lymphedema after axillary lymph node dissection. Early reports have suggested that ARM lymph nodes do not contain metastatic disease from breast cancer; however, these studies were conducted in early stage patients with low likelihood of lymph node metastasis. This study reported a phase 1 trial conducted in patients with cytologically documented axillary metastasis undergoing axillary lymph node dissection to determine the feasibility and oncologic safety of ARM.
Thirty patients, 23 (77%) of whom received preoperative therapy (chemotherapy in 22 patients and hormonal therapy in 1 patient), were enrolled. Blue dye was injected in the upper inner ipsilateral arm. The presence of blue lymphatics was noted, and blue lymph nodes were sent separately for pathologic evaluation.
The average time between blue dye injection and axillary exposure was 35 minutes (range, 15-60 minutes). Blue lymphatics were identified in 21 patients (70%) and blue lymph nodes in 15 patients (50%). The median number of ARM lymph nodes was 1 (range, 0-3 lymph nodes) and the median number of axillary lymph nodes was 26 (range, 6-47 lymph nodes). Axillary metastases were noted in 60% (18 of 30) of patients. Of 11 patients who had axillary metastasis and at least 1 ARM lymph node identified, 2 (18%) had metastasis to the ARM lymph node.
ARM appears to be a feasible technique with which to identify upper arm lymphatics during axillary surgery. However, the high prevalence of disease involving ARM lymph nodes in this small cohort suggested that preservation of these lymphatics is not oncologically safe in women with documented axillary lymph node metastasis from breast cancer.
The aim of axillary reverse mapping (ARM) is to preserve arm lymphatics in patients with breast cancer who underwent surgical axillary staging.
From June 2007 to December 2008, 49 patients who required axillary dissection (AD) underwent ARM. One milliliter of patent blue dye was injected in the ipsilateral arm, and all blue nodes identified during AD were sent separately for pathologic examination. Main variables associated with the detection rates of blue lymphatics, the pathologic status of blue and nonblue nodes, and the complications of the procedure were analyzed. Results Identification rates of blue lymphatics and blue nodes were 73.5% and 55.1%, respectively. Blue node identification was influenced by the time elapsed between injection of blue dye and surgery (P = .002) but not by the learning curve of the procedure. Although the blue node was clear of metastases in 24 of 27 patients, three patients with extensive nodal metastatic involvement (ie, pN2a and pN3a) showed breast cancer metastatic cells in the blue nodes as well. The only adverse effect of the procedure was skin tattooing at the injection site, which disappeared within 4 months in almost 80% of the procedures.
In patients with clinically negative axillary nodes, additional study is warranted to assess whether ARM may be used to spare the lymphatics from the arm. In the presence of extensive nodal disease, this technique may identify metastatic blue nodes, which demonstrates that there is not reliable separation of arm and breast lymphatic pathways.
The ARM technique was proposed to prevent arm lymphedema after ALND and/or SLN biopsy. However, several problems remain to be resolved in the practical application of this technique.
The fluorescent ARM nodes and/or lymphatics were identified using a fluorescence imaging system with subdermal injection of indocyanine green into the upper limb. ALND was performed in patients with clinically involved nodes, and the ARM nodes were separately removed during ALND. SLN biopsy was performed in patients with clinically uninvolved nodes. If SLN was positive, ALND was performed with removal of ARM nodes. Otherwise, identified ARM nodes were preserved unless they were the same as SLN.
ARM nodes and/or lymphatics were identified in 7 (88%) of 8 patients who underwent ALND, whereas they were identified in 9 (75%) of 12 patients who underwent SLN biopsy alone. ARM nodes were involved with tumors in 3 (43%) of the former patients, and SLN was the same as the ARM node in 2 (14%) of 14 patients who underwent SLN biopsy.
Fluorescence imaging was sensitive for identification of ARM nodes and/or lymphatics. However, further studies are needed before efforts to preserve these nodes can be safely implemented.
This pilot study evaluates the feasibility of axillary reverse mapping (ARM) during sentinel lymph node biopsy (SLNB) in breast cancer patients.
This study included 72 women with new breast cancer diagnosis, tumor size <2 cm, and clinically negative axilla. At the time of surgery, 2 mL of dermal blue patent were injected intradermally, subcutaneously, and intramuscularly in the ipsilateral upper inner arm in order to map and preserve the lymphatics of the arm. Blue arm lymphatics were preserved when in SLNB field. Microsurgical lymphatic-venous anastomosis (LYMPHA) was performed in women who underwent ALND.
In 27 of 72 patients (37.5%), the blue lymphatics draining the arm were observed in the SLNB field. In all these patients, the blue lymphatics were preserved. During ALND, the blue lymphatics draining the arm were visible in 8 out of 9 patients (88.9%); in all these women, the LYMPHA procedure was performed. All ARM blue nodes removed during ALND were negative for malignancy. At 9-month follow-up, no patient had lymphedema.
Arm lymphatic drainage can be observed in the SLNB field in 37.5% of the cases. Using the ARM during SLNB may facilitate the preservation of lymphatics draining the arm.
The purpose of this manuscript is to assess the efficacy of direct lymphatic venous microsurgery in the prevention of lymphedema following axillary dissection for breast cancer.
Nineteen patients with operable breast cancer requiring an axillary dissection underwent surgery, carrying out LVA between the blue lymphatics and an axillary vein branch simultaneously. The follow-up after 6 and 12 months from the operation included circumferential measurements in all cases and lymphangioscintigraphy only in 18 patients out of 19 cases.
Blue nodes in relation to lymphatic arm drainage were identified in 18/19 patients. All blue nodes were resected and 2-4 main afferent lymphatics from the arm could be prepared and used for anastomoses. Lymphatic-venous anastomoses allowed to prevent lymphedema in all cases. Lymphangioscintigraphy demonstrated the patency of microvascular anastomoses.
Disruption of the blue nodes and closure of arm lymphatics can explain the significantly high risk of lymphedema after axillary dissection. LVA proved to be a safe procedure for patients in order to prevent arm lymphedema.
The usefulness of routine axillary dissection (AD) at levels I-II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only.
One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000.
Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients.
SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.
Posttreatment morbidity within 1 year after sentinel node biopsy was evaluated objectively by physical examination and also by evaluating patients self-reports of symptoms in a questionnaire. These patients were compared with patients who underwent axillary clearance. At 2 weeks after surgery patients who had undergone sole sentinel node biopsy had made significantly better recoveries than those who had undergone axillary clearance. Although every fourth patient complained of at least mild arm symptoms 1 year after sole SNB, the risk of severe long-term morbidity is minimal. In particular, the risk of disabling lymphoedema seems to be negligible after SNB only.
Palmar-plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, fluorouracil, and capecitabine are the most frequently implicated agents. Recently, taxanes, especially docetaxel, have been widely used in combination with capecitabine in patients with metastatic breast cancer (MBC). A high percentage of PPE has been seen in patients undergoing this combination therapy. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence. Withdrawal or dose reduction of the implicated drug usually gives rise to amelioration of the symptoms. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve the pain. Use of systemic corticosteroids, pyridoxine (vitamin B6), blood flow reduction, and, recently, topical 99% dimethyl-sulfoxide have been used with variable outcomes. Vitamin E treatment has not been published before, especially without dose reduction of docetaxel-capecitabine therapy. Here we present five MBC patients treated with docetaxel-capecitabine combination therapy in whom PPE was observed during the clinical follow-up period. In all patients grade 2-3 PPE was observed. Vitamin E therapy was started at 300 mg/day p.o. without dose reduction of therapy and after 1 week of treatment PPE began to disappear. We suggest that it could be of interest to consider vitamin E as a preventive drug when drugs with a strong association with PPE are going to be administered.
The lymphatic system is perhaps the most complicated system of Homo sapiens. An introduction to the anatomy, embryology, and anomalies of the lymphatics is presented. The overall anatomy and drainage of the lymphatic vessels in outlined. The topographic anatomy, relations, and variations of the principle vessels of the lymphatic system (the right lymphatic duct, the thoracic duct, and the cisterna chyli) are presented in detail.
Despite the widespread use of the sentinel lymph node biopsy technique, many patients with invasive breast cancer still undergo an axillary lymph node dissection and are at risk of arm lymphedema. With the new awareness of lymphatic spread in the axillary nodes, it should be possible to define a new surgical approach between sentinel lymph node biopsy and complete axillary dissection, a procedure preserving specifically lymph nodes in relation to the arm.
Twenty-one patients with an operable breast cancer requiring an axillary dissection underwent surgery with an attempt to separate nodes related to the breast from specific nodes related to the arm. After an injection of blue dye in the arm, the surgeon performed the axillary dissection trying to identify blue nodes and ducts in order to preserve lymphatic arm drainage (LAD). If the blue nodes were located in the normal axillary dissection, they were removed separately.
In 15 of 21 patients (71%), blue nodes in relation with LAD were identified. In 10 (47%) patients, it was possible to dissect the LAD with the preservation lymphatic ducts. In 10 patients, the LAD nodes were removed: none of them contained metastases, despite the fact that the non-LAD axillary nodes contained metastases in 7 of 10 cases.
Identifying the LAD with blue dye injection in the arm is possible. A subsequent study can now begin to determine if this procedure is safe for patients and able to prevent lymphedema of the arm.
In order to evaluate the feasibility of dose-dense docetaxel followed by dose-dense AC (doxorubicin/cyclophosphamide) as adjuvant chemotherapy for operable breast cancer, we conducted a phase II study.
In cohort 1, 28 patients received docetaxel 100 mg/m2 followed by doxorubicin 60 mg/m2 with cyclophosphamide 600 mg/m2, each every 2 weeks for 4 weeks (total of 8 cycles). Enrollment was discontinued because of stopping criteria based on significant toxicity (grade 4 hematologic toxicity or grade >or= 3 nonhematologic toxicity). In cohort 2, the docetaxel dose was reduced to 75 mg/m2; enrollment was discontinued after 18 patients.
Significant toxicity occurred in 79% and 72% of patients in cohorts 1 and 2, respectively, resulting in treatment delays in 50% and 17% of patients, respectively. The most common grade 4 hematologic toxicity was neutropenia, which occurred in 7% and 42% of cohort 1 patients during docetaxel and AC, respectively, and in none and 19% of cohort 2 patients, respectively. The most common grade >or= 3 nonhematologic toxicity was palmar-plantar erythrodysesthesia, which occurred in 25% and none of cohort 1 patients during docetaxel and AC, respectively. With docetaxel 75 mg/m2 and patient education encouraging routine use of topical strategies, grade 3 palmar-plantar erythrodysesthesia occurred in only 11% of cohort 2 patients. Grade 2 nail changes were also debilitating and occurred in 33% of cohort 1 patients during AC.
These phase II findings suggest that dose-dense docetaxel 100 mg/m2 followed by AC is not feasible and, until more studies are conducted, should be restricted to clinical studies.