Download PDF
Review  |  Open Access  |  27 May 2024

Breast reconstruction and breast cancer-related lymphedema: insights and perspectives

Views: 150 |  Downloads: 19 |  Cited:   0
Plast Aesthet Res 2024;11:17.
10.20517/2347-9264.2024.32 |  © The Author(s) 2024.
Author Information
Article Notes
Cite This Article

Abstract

An estimated 500,000 women were diagnosed with the debilitating breast cancer-related lymphedema (BCRL) in 2022. Lymphedema is not just fluid, but a complex disease characterized by low-grade inflammation, fat deposition, and fluid accumulation, severely affecting patients’ quality of life (QoL). The impact of surgical and adjuvant breast cancer treatment on BCRL has been investigated, and treatments have been modified to maintain a high cancer-free survival while addressing the late effects. In addition, the demand for breast reconstruction has increased in the last two decades, leaving a gap in the understanding of the association between BCRL and breast reconstruction. Early detection and treatment of BCRL is crucial in preventing advancement into an impairing chronic stage, making reliable diagnostic modalities necessary. This review is an updated overview of the various diagnostic tools and the established and evolving treatment approaches for BCRL, providing insight into the research findings published since 2017 on breast reconstruction and BCRL through a systematic literature search. Based on the reviewed literature, the authors could not conclude any sure causality between BCRL and breast reconstruction. Studies suggest that breast reconstruction contributes to lower BCRL rates, but prospective observational studies are recommended for future research.

Keywords

Breast reconstruction, breast cancer-related lymphedema, late morbidity, cancer survivor

INTRODUCTION

Nearly 2.3 million women were diagnosed with breast cancer in 2022[1]. As mortality rates have decreased[2,3], a growing number of women suffer from the long-term effects of breast cancer and its treatment. As an oncologist, plastic-, or breast surgeon treating women diagnosed with breast cancer, it is crucial to understand the relationship between cancer treatment, patient-related outcomes, and pertinent strategies to prevent or treat long-term effects, such as BCRL. This narrative review aims to provide insight into BCRL following breast reconstruction, addressing current knowledge about the association between breast reconstruction and BCRL. The scope is perspectives on the pathophysiological and clinical implications of BCRL, including a discussion on how oncologic breast surgery and adjuvant treatment impact the risk of developing BCRL. The review also highlights advancements in diagnostics and treatment over the last decade. Literature was systematically searched from EMBASE, Pubmed, Cochrane, and BASE databases from January 2017 to December 2023 for breast reconstruction and BCRL articles. Since no international checklist is published for narrative reviews, we adhered to the Scale for the Assessment of Narrative Review Articles (SANRA)[4].

BREAST CANCER-RELATED LYMPHEDEMA

Secondary lymphedema may arise from surgical procedures, radiation, trauma, or infection. Nevertheless, the predominant cause is breast cancer[5]. The incidence of BCRL exhibits considerable variability throughout the literature[6-9]. The most recent systematic review reports an incidence of 21.9%[10]. Thus, approximately half a million women diagnosed with breast cancer in 2022 may potentially be diagnosed with lymphedema during their lifetime.

PATHOPHYSIOLOGY

Lymphedema is characterized by the accumulation of protein-rich fluid, resulting in swelling of the affected body part. The lymphatic vessels return around 2-4 L of fluid to the venous system daily[11]. An imbalance occurs when the lymphatic load exceeds the transport capacity, resulting in lymphedema. However, the pathophysiology of lymphedema is more complex than excess fluid in the interstitial space.

The collecting lymphatic vessels are located in the subcutaneous adipose layer. Thus, lymph fluid accumulates between adipocytes, resulting in adipose hyperplasia or hypertrophia[12]. The exact pathway from increased lymph fluid to hyperplasia or hypertrophia of adipocytes is not fully understood[13], and consensus on whether adipocytes increase in size due to lymphedema is absent[13-15]. Nevertheless, lymphedema leads to the deposition of adipose tissue[16].

Non-linear lymphatic anatomy and early disturbance in lymphatic transport are risk factors for the development of BCRL[17,18]. The role of growth factors, such as vascular endothelial growth factor (VEGF)-C, has been debated[19,20], and treatment with VEGF-C adenovirus was applied in a randomized clinical trial, with ambiguous results[12,21]. The deposition and remodeling of adipose tissue in lymphedema patients may contribute to increased low-grade local inflammation due to the secretion of pro-inflammatory cytokines[22,23]. This chronic inflammation, in which CD4+ cells play a crucial role[21,24,25], has been demonstrated to facilitate fibrosis during the progression to more advanced stages of lymphedema. Pathohistological studies have identified hyperplasia of collagen fibers and smooth muscle cells, causing thickening of the lymphatic vessels. This contributes to the hardening of the lymphatics, compromising their peristaltic ability and[26-28], lastly, exacerbating the accumulation of lymph. In summary, the pathophysiology of lymphedema results from an inappropriate circle of stasis, causing an imbalance in the interstitial fluids, lymphatic vessel remodeling and function, and adipose tissue deposition.

CLINICAL AND PSYCHOLOGICAL IMPLICATIONS OF BREAST CANCER-RELATED LYMPHEDEMA

Symptoms of arm lymphedema may manifest as swelling, stiffness, pain, heaviness, and restricted movement[29,30]. When examining chronic pain after breast cancer, BCRL was found to be the highest risk factor for developing chronic pain[31,32]. A recently published study on breast reconstruction and upper-extremity function found patients who developed lymphedema to be approximately four times more likely to report high scores on the disabilities of the arm, shoulder, and hand (DASH) questionnaire, signifying upper extremity dysfunction that affect the activity of daily living (ADL)[33]. A systematic review of QoL showed that breast reconstruction improves QoL after mastectomy[34]. However, another study found that BCRL possibly negates the positive effect of breast reconstruction[35].

Psychological stress after breast cancer is reported with a range between 22% and 50% in the literature[36,37]. In a recent German study, 67.3% of patients reported high stress levels, associating BCRL with increased distress[38]. In addition, a matched cohort study from 2023 confirmed that patients with BCRL exhibited lower levels of psychosocial well-being[39]. Consequently, BCRL and upper limb morbidity emerge as the primary complications that negatively impact work activity with increased sick leave days and, lastly, increased socioeconomic burden[40-44].

DIAGNOSTIC MODALITIES

Lymphedema may manifest several years after breast cancer surgery. A study published in 2017 found that 13.5% presented with lymphedema at their two-year follow-up[45], which increased to 41.1% when patients were examined after ten years[45]. A recent cross-sectional study found the median time from breast cancer diagnosis to lymphedema to be four years[46], suggesting both a potential delay in diagnosis and an evolution in limb physiology.

Various diagnostic criteria are present in the literature, encompassing highly advanced technologies, such as 3D live images of lymph flow with SPECT-CT lymphoscintigraphy[47,48], to simple methods, such as circumference measurements and patient-reported outcome measures [Table 1][49-72]. Reliable and valid assessment tools for BCRL are imperative for diagnosing, monitoring, and comparing treatment responses[73]. Lymphoscintigraphy has replaced water displacement as the gold standard, and indocyanine green angiography (ICG-A) is likely the next modality[74]. While the presence of dermal backflow in lymphoscintigraphy is accepted as one of the diagnostic criteria for lymphedema, newer imaging techniques have yet to establish their clear diagnostic criteria for lymphedema. However, a 10% difference between the ipsilateral arm, forearm, or both compared to the contralateral side or baseline measurements is often used as a cut-off value. Notably, the validity of lymphedema diagnosis without baseline measurements is questionable, as studies have shown a significant variation in volume between the two arms at baseline[75,76]. In conclusion, a missing baseline measurement can lead to misdiagnosis in around 40% of patients[75], making baseline measurements imperative in clinical and academic settings to minimize the risk of under or over-diagnosing lymphedema.

Table 1

Diagnostic methods of arm lymphedema in recent literature

Diagnostic methodDescriptionAdvantagesLimitations
Water displacementImmersion of whole limb in water, measuring the volume of water displaced by the submerged limbSensitive and specific
High interclass correlation
Messy and difficult
Inability to localize to specific limb segments
It cannot be used if there are open wounds
Tape circumferential measurementMeasurement of limb circumference, often multiple places along the armInexpensive
In-home application is possible
Easy
High intra- and inter-rater variability
Volume calculation assumes a circular arm form, which is seldom the case
PerometryInfrared light measures limb volume and collects two-dimensional information from each armHygienic
Creates a 3D image of the limb, enabling localization of swelling
Can detect a 3% volume change
Useful for bilateral lymphedema
Requires specialized equipment
Cost
Can only measure limb edema (e.g., Not breast edema)
Bioimpedance spectroscopy (BIS)Uses electrical current to scan the upper extremities, measuring resistance Requires minimal training
Rapid
Accurate
Quantitative assessment
Equipment availability
Requires trained personnel
Not applicable for bilateral lymphedema
Limitations in advanced lymphedema due to fat-dominant composition
Dual-energy X-ray absorptiometry (DEXA)Measures chemical limb compositionQuantitative assessment Distinguishes fat and fluidRadiation exposure
Limited availability
LymphoscintigraphyRadioactive tracer imaging of the lymphatic systemVisualizes lymphatic flow and lymph nodes
Identifies lymphatic damage
Invasive
Radiation exposure
Limited availability
Magnetic resonance imagingUses magnetic fields and radio wavesExcellent soft tissue contrast
Detailed anatomical images of fat, muscle and water
Can be used as MR lymphangiography
Can detect changes in edema much earlier than most other modalities
Expensive
Limited availability
MR cannot resolve smaller lymphatic channels due to limitations in resolution
Indocyanine green (ICG) Intradermal injection of fluorescent ICG visualizes lymphatic vessels with a near-infrared camera (NIR)Real-time imaging Assesses lymphatic function
No radiation
Visualizes dermal backflow
Limited penetration depth of 1.5 cm
Operator-dependent
With NIR: Depth visualization of 3-4 cm
Photoacoustic imagingLight energy generates ultrasound waves, which a transducer depicts as an image Real time
Portable
Needs imaging contrast, such as ICG or Evans blue, to view lymphatics
Computed tomography (CT)X-ray technology for cross-sectional imagesDetailed images
3-D representation
Evaluates anatomical structures
Radiation exposure
Limited sensitivity for lymphedema
Three-dimensional laser scannerLaser-based scanning for surface measurementsPrecise surface mapping
Higher intra-rater reliability compared to water displacement
Limited to surface measurements
May not assess deep tissues
High cost of the device
Time-consuming
UltrasoundHigh-frequency sound waves for imaging and blood flowCan measure texture and characterize edema
Few limitations to depth perception
Easy to transport
Operator dependence
Limited depth perception for ultra-high frequency (rarely used)
Tissue dielectric constant (TDC)300 MHz is emitted into the tissue, and a wave is returned with information on local water content Provides a better understanding of arm spatial variability in relation to girth measures
Convenient
Non-invasive
Interpretation of values may depend on location and total body water percentage

Multiple staging systems for lymphedema exist, with the International Society of Lymphedema (ISL) staging system being the most widely used [Table 2][12,76-78].

Table 2

Staging of lymphedema according to ISL

Clinical presentationPathophysiology
Stage 0
Latent or subclinical
No visible sign of swelling
Subjective symptoms might be present
Lymphatic insufficiency/impaired lymph transport
Subtle changes in fluid composition
Stage 1
Spontaneously reversible
Pitting may occur
Possibly hyperkeratosis
Early accumulation of fluid
High in protein
ICG shows dilated lymphatics with irregular pulsation
Dermal backflow
Stage 2
Spontaneously irreversible
Pitting is still present, but the arm is firmer than in stage 1 Increased fibrosis and tissue changes, including accumulation of adipocytes
Stage 3
Lymphostatic elephantiasis
No pitting
Skin changes: thickening and hyperkeratosis
Possible warty overgrowths
Irreversible swelling with significant tissue fibrosis
Chronic inflammation
ICG will often show diffuse accumulation of dye in the skin

ONCOLOGIC BREAST SURGERY - SURGICAL INTERVENTION FOR THE TREATMENT OF BREAST CANCER

Oncologic breast surgery has evolved significantly since Halsted’s initial introduction of the radical mastectomy in 1882[79]. Breast-conserving surgery (BCS) is widely used instead of mastectomy for early breast cancer. A meta-analysis including 25 studies[80] concluded that BCS is superior to mastectomy for early breast cancer. Still, mastectomy is the surgical choice for many patients, especially in low and middle-income countries, where access to adjuvant therapy is limited[81,82]. Conversely, western countries are increasingly aiming to avoid breast deformities and achieve contralateral symmetry by applying oncoplastic surgery with volume displacement or replacement techniques.

LYMPH NODE DISSECTION

Assessment of the lymph nodes is a crucial part of breast cancer treatment. The risk of developing lymphedema and other arm morbidities is highly dependent on the extent of the axillary surgery, as demonstrated by a recent study analyzing the risk of BCRL[83]. Studies indicate that women undergoing axillary lymph node dissection (ALND) - both with and without adjuvant radiotherapy - have a significantly higher incidence of lymphedema compared to patients undergoing sentinel lymph node biopsy (SLNB) under the same conditions[10,70,83-86]. However, BCRL is still reported after SLNB with postmastectomy radiation therapy (PMRT)[87] and increasing BMI as reported risk factors[83].

RADIOTHERAPY

PMRT and lymphedema have been extensively examined, with multiple trials assessing the difference in toxicity of different radiation schedules[88-94]. A review and meta-analysis from 2020 showed that while PMRT serves its purpose of decreasing local and regional recurrence of breast cancer, it also plays a key role in the development of lymphedema[95].

The impact of radiation on breast reconstruction was recently investigated; a meta-analysis found immediate autologous free flap reconstruction to be associated with superior flap survival compared to delayed autologous reconstruction, indicating that autologous immediate breast reconstruction (IBR) is safe even when PMRT is planned[96]. However, a large cohort study from 2020 found PMRT to increase the 5-year cumulative complication rate for both autologous, two-stage implant-based, and direct-to-implant reconstruction types[97]. The outcome of a direct-to-implant breast reconstruction relies on the mastectomy skin flap viability, and even though modalities - such as ICG-A - lowered the rate of mastectomy skin necrosis[98], the intraoperative decision to deter from one-stage implantation to an expander could potentially bias the complication outcome. Ultimately, the decision on the type of reconstruction should not solely rely on a single factor, such as PMRT.

BREAST RECONSTRUCTION

Breast reconstruction surgery has become a significant part of the breast cancer pathway, with the primary aim of breast reconstruction to improve QoL and breast-related satisfaction for the patient. Increased information, a rise in risk-reducing mastectomies[99], changes in legislation in some countries, such as the United States[100], and the suggestion that breast reconstruction increases health-related QoL outcomes after mastectomy[34], all contribute to the explanation behind the worldwide increase in demand for breast reconstruction during the last two decades[101-103]. The number of patients opting for reconstruction has generally risen but varies between countries, with rates of approximately 18% in Australia[104], 30% in Sweden[105], 40% in Denmark[106], and 50% in South Korea[103].

TIMING OF THE RECONSTRUCTION

Several studies have investigated the timing of breast reconstruction and found IBR to be preferable when looking at the psychosocial impact, as well as the socioeconomic cost of breast reconstruction[107-112]. Considering the rate of complications, IBR has been associated with significantly higher complication rates than delayed procedures[113]. Nevertheless, Saheb-Al Zamani et al. could only confirm the higher complication rate for implant-based but not autologous reconstructions[114], and other studies found no significant difference in flap loss between IBR and delayed breast reconstruction (DBR)[115,116]. The latest meta-analysis concluded that IBR generally increases the risk of complication, but additional prospective and observational studies are needed to assess if one reconstructive technique is superior to another[117]. QoL has increasingly been examined as an outcome in studies assessing the difference between IBR and DBR, and no difference in postoperative QoL between IBR and DBR was found[118,119].

AUTOLOGOUS AND IMPLANT-BASED BREAST RECONSTRUCTION

Autologous reconstruction was found to improve upper extremity outcomes in patients undergoing breast reconstruction[33]. Dauplat et al. found latissimus dorsi (LD) flaps to have the lowest risk of major complication compared to implant alone, LD flap with implant, or the transverse rectus abdominus myocutaneous (TRAM) flap[31]. There are multiple options for reconstruction. However, the right choice of reconstruction method depends on several factors, including donor-site availability, medical history, previous oncologic treatment, and most importantly, the patient’s preferences. Reports have shown that implant-based reconstruction is the more commonly used technique[120,121].

One of the more dreaded complications in free flap breast reconstruction is venous congestion. Therefore, additional venous drainage using the cephalic vein is sometimes incorporated into the flap. It is currently unclear if this increases the risk of ipsilateral lymphedema, although Svee et al. did not find an increased risk[122]. In this relation, it is, however, relevant to note that their sample size was small and that another group found lymphedema to develop or worsen when using the cephalic vein[123].

BREAST CANCER-RELATED LYMPHEDEMA AND BREAST RECONSTRUCTION

The most recent systematic review on the impact of breast reconstruction on BCRL from 2017 concluded that breast reconstruction was associated with lower rates of lymphedema[124]. However, due to high heterogenicity in the included studies, further prospective studies were deemed necessary to identify the mechanism by which breast reconstruction contributes to reduced rates of lymphedema.

In our systematic literature search, 23 studies, including a total of 85,584 patients, were published since the review by Siotos et al. on BCRL and breast reconstruction[124]. In various studies, the incidence of lymphedema was found to be lower in cases with breast reconstruction compared to mastectomy alone[125-134], while other studies did not specify the incidence of lymphedema for breast reconstruction[31,122,135-139], type of reconstruction[128,129,140], or BCRL incidence at all[31]. Figure 1 presents an overview of the incidence reported for BCRL in the different studies, where possible, by reconstruction type. Further aspects emerged from the studies:

Breast reconstruction and breast cancer-related lymphedema: insights and perspectives

Figure 1. Incidence of BCRL in included studies from 2017-2024 reporting incidence of BCRL for breast reconstruction. § Significantly reduced (↓) incidence of BCRL compared to other selected groups with a higher incidence of BCRL (↑); ‡ Significantly reduced incidence of BCRL for patients who had ALND and chemotherapy; † Full text not available. Data are based on the abstract. BCRL: breast cancer-related lymphedema; ALND: axillary lymph node dissection; LD: latissimus dorsi; DIEP: deep inferior epigastric perforator; OR: Odds Ratio.

Two recent large cohort studies published only as abstracts have found that delayed breast reconstruction (DBR) is significantly associated with reduced BCRL within ten years[127,131]. Both cohorts were extracted from the same 85,776,922 de-identified patient records. In one cohort, 60,157 patients met the inclusion criteria; in the other cohort, only 24,136 patients did. As the smaller of the two cohort studies analyzed both implant vs. autologous and delayed vs. immediate breast reconstruction, while the larger study analyzed only autologous flaps, we question the inclusion criteria for the two studies. A recent prospective study of delayed and immediate autologous reconstruction found that out of the seven patients with pre-reconstruction lymphedema[134], three patients experienced an improvement that could also be measured, and one patient felt the lymphedema worsened.

A 2021 study investigating arm volume increase also explored the difference between lumpectomy, mastectomy, and IBR on lymphedema and found a lower BCRL incidence for the IBR group compared to the mastectomy and lumpectomy group[129]. Follow-up was limited to one year, and it would be interesting to study how many patients in the low-volume group will develop clinical lymphedema and assess if this impacts the relative incidence of surgery type. The study was one of the few with baseline measurements of lymphedema, as only six out of 23 studies reported baseline measurements[70,122,134,140,141]. All six studies were prospective cohort studies with smaller cohort numbers compared to the three largest retrospective cohorts that included 24,136[127], 60,157[131], and 5,497[126] patients, respectively. The largest of the prospective studies was performed by a research group from Massachusetts General Hospital and included 327 patients with a total of 578 reconstructed breasts[140]. Here, the researchers did not find any significant impact of breast reconstruction on BCRL.

In a more recently published cross-sectional study, the average follow-up of 38 months was surpassed[135], with a mean long-term follow-up of 10.5 years. Laws et al. examined the disparities between implant-based and autologous IBR in their analysis, stratifying the results based on axillary intervention and PMRT. However, the study did not specify the arm symptoms present in the different groups, precluding an opportunity to report the incidence of BCRL.

Two studies reported a relatively high incidence of BCRL for patients treated with breast reconstruction compared to other studies[70,142]. However, the study with the highest BCRL incidence after breast reconstruction only included five patients with breast reconstruction and concluded there was no significant difference in the effect of surgery type on BCRL[70]. The other study included 72 patients but did not describe how or when they measured lymphedema[142] - only that the diagnosis was based on physical examination[142]. Unfortunately, this lack of description of measurement methods or diagnostic criteria was observed for some of the studies[131,138]. Diagnostic methods used in other studies were circumference[126,136,143], bioimpedance spectroscopy (BIS)[70,134,141], and perometry[129,140]. Several studies also included patient symptoms in evaluating whether lymphedema was present [128,132,135].

A study from 2017 investigated the effect of IBR on lymphedema and further elaborated on the difference between implant-based and autologous IBRs[144]. Here, the researchers found a statistically lower rate of BCRL for immediate DIEP and LD flaps compared to patients receiving implant-based breast reconstruction despite a higher rate of ALND in the LD flap group. Women in the autologous group had a higher BMI, had more radiotherapy preoperatively, and were older, which all are demographic factors associated with an increased risk of BCRL. When correlating to ALND, the researchers found that autologous breast reconstruction significantly reduced BCRL for patients who had ALND and received chemotherapy. Only one study reported the effect of oncoplastic surgery, where no arm lymphedema was found[141].

EVOLVING TREATMENT APPROACHES FOR LYMPHEDEMA

Early detection and management of lymphedema, clinical as well as subclinical, at an early stage, is imperative in preventing its advancement to a chronic stage. However, this narrative review has unveiled the disparity among criteria used to diagnose lymphedema, leading to delayed detection and subsequent treatment initiation. Clinicians lack superior treatment options considering patient preferences, resources, and clinical settings. The following subsections address the currently available treatment modalities and emerging treatment strategies.

Decongestive techniques

Treatment of subclinical lymphedema with compression garments, as seen in Figure 2, was shown to be effective[145]. Compression garments are often combined with manual lymphatic drainage (MLD), therapeutic exercise, moisturizing skincare, and patient education; This combination of five modalities is referred to as complex decongestive physical therapy[146]. Several randomized trials and systematic reviews with meta-analyses found that manual lymphatic drainage, a compression pump, or exercise do not lead to volume reduction[147-150]. Conversely, several systematic reviews with meta-analyses present significant volumetric changes due to MLD[151,152], complex physical/decongestive therapy (CDT)[153], compression pump[154], and laser therapy[155]. In addition, a systematic Cochrane review found MLD to be safe and beneficial to compression bandaging for volume reduction in patients with mild-to-moderate BCRL[156].

Breast reconstruction and breast cancer-related lymphedema: insights and perspectives

Figure 2. Treatment of subclinical lymphedema with compression garments.

Rafn et al. presented a statistically significant effect in volume reduction across all interventions (MLD, compression pump, exercise, kinesio taping, laser, and acupuncture) compared to any control. Notably, most of the systematic reviews had chosen volumetric changes as their primary outcome and not the most frequently reported arm symptom associated with BCRL, namely pain. However, no systematic reviews and meta-analyses found an effect of either MLD[153,157], laser therapy[152,155,157,158], CDT[153], kinesio taping[159], or water-based exercise on pain or discomfort[146,160]. In conclusion, no clear advantage was seen for any treatment methods, regardless of whether the comparison was made with active or non-active control conditions.

Surgical treatment modalities and emerging therapies and research

Complete decongestive therapy has for many years been the primary treatment[161]; however, microsurgical techniques were implemented in the treatment of lymphedema in the seventies, where lymphatic venous anastomosis (LVA) was first used to treat postoperative lymphedema[162]. Since then, multiple studies on LVA have been undertaken[163-165]. A smaller study involving ten patients undergoing LVA from 2008 showed minimal reduction in lymphedema volume and only minimal improvement in QoL[166]. However, a case series of 20 patients by Chang et al. showed a reduction in lymphedema volume of 35% and a 95% improvement in lymphedema symptoms after one year[167]. A larger study involving 169 BCRL patients undergoing autologous lymph vessel transplantation from the ventromedial lymphatic bundle at the patient’s thigh to the upper limb found that microsurgical technique significantly and persistently improved lymph drainage in patients with lymphedema[168]. Recently, a systematic review found 102 studies investigating LVA, concluding that LVA can reduce the severity of secondary lymphedema[169]; however, standardization of reporting is needed to allow further comparability between methods and studies. LVA has recently emerged as a preventive therapy, where axillary reverse lymphatic mapping and immediate lymphaticovenous bypass are increasingly used in the operating room worldwide[170]. Several studies report a lower prevalence of BCRL in cohorts where lymphaticovenous bypasses were performed as a preventive approach[171-177]. Nevertheless, not all studies confirmed the long-term effects of the Lymphatic Microsurgical Preventive Healing Approach (LYMPHA) on BCRL[178].

Another surgical technique is the vascularized lymph node transfer (VLNT) from other areas in the body. Inguinal lymph node transfer was first shown to reduce lymphedema of the leg in 1982[179], and later, Becker et al. reported a decrease in lymphedema after inguinal lymph node transfer to the axilla in 20 out of 22 patients[180]. The vascularized omental lymph node transfer (VOLT) flap to the axillae was first published by Nakajima in 2006[181]; a systematic review has found VOLT improves lymphedema, but it highlights that further studies are needed to identify appropriate patients for the technique[182]. One advantage of the VOLT flap is that the removal of the omentum does not induce iatrogenic lymphedema at the donor site[183], which is a risk with lymph node transfer from the inguen or axillae[184]. This risk can potentially be reduced using ICG-A and lymphoscintigraphy preoperatively, as proposed by Pons et al.[185]. Recently, Teven et al. performed a minimally-invasive approach utilizing the da Vinci Single-Port robotic system, only requiring two port holes[186], but there is an ongoing debate on the appropriate method of harvesting the flap[183].

Combining surgical and decongestive approaches has recently been investigated, where a study found LVA combined with compression therapy to improve cellulitis in early-stage BCRL[187]. Another study combined CDT and MLD with either LVA or VLNT, dependent on patient anatomy, for stage I and II lymphedema[188]. For stage III lymphedema, patients also had suction-assisted lipectomy, which previous studies showed to reduce lymphoedema in the arm and be an effective technique in end-stage lymphedema[189,190]. 10 of the patients included had combined breast reconstruction with DIEP flaps and VLNT[188]. No difference in complication rate between GE-VLNT and GE-VLNT combined with DIEP was found in seroma, dehiscence, and lymph node flap loss[188].

In recent years, the combination of breast reconstruction with lymphedema surgery in a single surgery has been explored. A retrospective chart review found VLNT to have a similar complication profile with or without autologous breast reconstruction[191]. A 2020 study by Chang et al. showed that combining the DIEP flap with VLNT combined with lymphaticovenous anastomosis was safe and might be superior to VLNT alone[192]. The patients were followed up 12 months post-operatively, both cohorts improved their lymphedema symptoms. A recent review found a higher risk of seroma, wound problems, and donor site pain when comparing VLNT combined with autologous breast reconstruction and isolated VLNT[193]. However, as they report, surgical expertise with VLNT is increasing, and the incidence of seroma has decreased for their own cohort during the last five study years[193]. Taranto et al. compared delayed breast reconstruction using DIEP flaps with and without VLNT and found no significant difference in donor site complication rate, no difference in BREAST-Q scores, but a notable circumference reduction in the lymphedema arm and statistically significant improvement in lymphedema QoL questionnaire (LYMQOL) after surgery[194].

PERSPECTIVES

When deciding what kind of treatment and follow-up program breast cancer patients should follow in a specific country, economics and feasibility will naturally influence the decision, as resources are divided unevenly around the world. Newer prediction strategies, such as the utilization of artificial intelligence (AI), could help physicians decide on which patients should be monitored more closely[195], or perhaps benefit from preventive BCRL surgery. However, AI is limited by the data it is built on, and it is therefore essential to produce and publish data of high quality, both negative and positive findings, to strengthen these computational tools.

CONCLUSION

Based on the current review of the literature, no certain causality between BCRL and breast reconstruction was found. The surgical and oncologic treatment modalities for breast cancer, as well as patient BMI, are likely factors impacting the advent of BCRL. Recent studies suggest that breast reconstruction may contribute to lower rates of lymphedema compared to mastectomy alone. The increased awareness of BCRL should encourage the reporting and publishing of data on this dreaded complication, providing the clinical and scientific community with the opportunity to perform meta-analyses. Further research, especially prospective studies with baseline measurements, is needed to fully address the impact of breast reconstruction treatment modalities on lymphedema, thus providing the breast reconstruction team with an increased insight into the complexity of lymphedema.

DECLARATIONS

Acknowledgments

Thanks to Professor Andreas Hougaard Laustsen-Kiel for English proofreading.

Authors’ contributions

Contributed substantially to the study’s conception and design: Laustsen-Kiel CM, Hansen L, Lauritzen E, Damsgaard TE

Wrote the main manuscript, and performed data acquisition, data analysis and interpretation: Laustsen-Kiel CM, Hansen L

Read, critically appraised, and approved the final manuscript: Laustsen-Kiel CM, Hansen L, Lauritzen E, Damsgaard TE

Availability of data and materials

Not applicable.

Financial support and sponsorship

This work was supported by the Vissing Foundation, grant number: 519140 AHO/LAX.

Conflicts of interest

All authors declare that there are no conflicts of interest. Tine Engberg Damsgaard is an Editorial Board member of the journal Plastic and Aesthetic Research. AI and AI-assisted technologies have been used in the writing process of the manuscript.

Ethical approval and consent to participate

Not applicable.

Consent for publication

Written permission was obtained from the patient for the use of photographs.

Copyright

© The Author(s) 2024.

REFERENCES

1. The International Agency for Research on Cancer World Health Organization. Cancer today. Available from: https://gco.iarc.who.int/today/files/803/pie.html [Last accessed on 22 May 2024].

2. Carioli G, Malvezzi M, Rodriguez T, Bertuccio P, Negri E, La Vecchia C. Trends and predictions to 2020 in breast cancer mortality in Europe. Breast 2017;36:89-95.

3. Arnold M, Morgan E, Rumgay H, et al. Current and future burden of breast cancer: global statistics for 2020 and 2040. Breast 2022;66:15-23.

4. Baethge C, Goldbeck-Wood S, Mertens S. SANRA-a scale for the quality assessment of narrative review articles. Res Integr Peer Rev 2019;4:5.

5. Brix B, Sery O, Onorato A, Ure C, Roessler A, Goswami N. Biology of lymphedema. Biology 2021;10:261.

6. Armer JM, Ballman KV, McCall L, et al. Lymphedema symptoms and limb measurement changes in breast cancer survivors treated with neoadjuvant chemotherapy and axillary dissection: results of American college of surgeons oncology group (ACOSOG) Z1071 (Alliance) substudy. Support Care Cancer 2019;27:495-503.

7. Naoum GE, Roberts S, Brunelle CL, et al. Quantifying the impact of axillary surgery and nodal irradiation on breast cancer-related lymphedema and local tumor control: long-term results from a prospective screening trial. J Clin Oncol 2020;38:3430-8.

8. Swaroop MN, Ferguson CM, Horick NK, et al. Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: results from a large prospective cohort. Breast Cancer Res Treat 2015;151:393-403.

9. Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. The epidemiology of arm and hand swelling in premenopausal breast cancer survivors. Cancer Epidemiol Biomarkers Prev 2007;16:775-82.

10. Shen A, Lu Q, Fu X, et al. Risk factors of unilateral breast cancer-related lymphedema: an updated systematic review and meta-analysis of 84 cohort studies. Support Care Cancer 2022;31:18.

11. Barrett KE, Barman SM, Boitano S, Brooks H. Ganong's review of medical physiology 25th edition: 25th edition. Available from: https://www.mheducation.com/highered/product/ganong-s-review-medical-physiology-25th-edition-barrett-brooks/9780071826457.html [Last accessed on 22 May 2024].

12. Brown S, Dayan JH, Kataru RP, Mehrara BJ. The vicious circle of stasis, inflammation, and fibrosis in lymphedema. Plast Reconstr Surg 2023;151:330e-41e.

13. Koc M, Wald M, Varaliová Z, et al. Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors. Sci Rep 2021;11:8171.

14. Tashiro K, Feng J, Wu SH, et al. Pathological changes of adipose tissue in secondary lymphoedema. Br J Dermatol 2017;177:158-67.

15. Zhang J, Hoffner M, Brorson H. Adipocytes are larger in lymphedematous extremities than in controls. J Plast Surg Hand Surg 2022;56:172-9.

16. Hoffner M, Peterson P, Månsson S, Brorson H. Lymphedema leads to fat deposition in muscle and decreased muscle/water volume after liposuction: a magnetic resonance imaging study. Lymphat Res Biol 2018;16:174-81.

17. Kinney JR, Friedman R, Kim E, et al. Non-linear lymphatic anatomy in breast cancer patients prior to axillary lymph node dissection: a risk factor for lymphedema development. J Mammary Gland Biol Neoplasia 2023;28:20.

18. Thomis S, Devoogdt N, Bechter-Hugl B, Fourneau I. Early disturbance of lymphatic transport as a risk factor for the development of breast-cancer-related lymphedema. Cancers 2023;15:1774.

19. Yan A, Avraham T, Zampell JC, Aschen SZ, Mehrara BJ. Mechanisms of lymphatic regeneration after tissue transfer. PLoS One 2011;6:e17201.

20. Slavin SA, Van den Abbeele AD, Losken A, Swartz MA, Jain RK. Return of lymphatic function after flap transfer for acute lymphedema. Ann Surg 1999;229:421-7.

21. Ogata F, Fujiu K, Matsumoto S, et al. Excess lymphangiogenesis cooperatively induced by macrophages and CD4+ T cells drives the pathogenesis of lymphedema. J Invest Dermatol 2016;136:706-14.

22. Antoniak K, Hansdorfer-Korzon R, Mrugacz M, Zorena K. Adipose tissue and biological factors. Possible link between lymphatic system dysfunction and obesity. Metabolites 2021;11:617.

23. Azhar SH, Lim HY, Tan BK, Angeli V. The unresolved pathophysiology of lymphedema. Front Physiol 2020;11:137.

24. Mehrara BJ, Park HJ, Kataru RP, et al. Pilot study of anti-Th2 immunotherapy for the treatment of breast cancer-related upper extremity lymphedema. Biology 2021;10:934.

25. Zampell JC, Yan A, Elhadad S, Avraham T, Weitman E, Mehrara BJ. CD4+ cells regulate fibrosis and lymphangiogenesis in response to lymphatic fluid stasis. PLoS One 2012;7:e49940.

26. Mihara M, Hara H, Hayashi Y, et al. Pathological steps of cancer-related lymphedema: histological changes in the collecting lymphatic vessels after lymphadenectomy. PLoS One 2012;7:e41126.

27. Nuri T, Jin D, Takai S, Ueda K. Tryptase-positive mast cells promote adipose fibrosis in secondary lymphedema through PDGF. Curr Issues Mol Biol 2023;45:8027-39.

28. Ogata F, Fujiu K, Koshima I, Nagai R, Manabe I. Phenotypic modulation of smooth muscle cells in lymphoedema. Br J Dermatol 2015;172:1286-93.

29. Hara Y, Otsubo R, Shinohara S, et al. Lymphedema after axillary lymph node dissection in breast cancer: prevalence and risk factors-A single-center retrospective study. Lymphat Res Biol 2022;20:600-6.

30. Thomas M, Pike C, Humphreys I, Bragg T, Ghattaura A. Impact and outcomes after lymphaticovenous anastomosis for 150 cases of lymphoedema followed up over 24 months. J Plast Reconstr Aesthet Surg 2023;85:104-13.

31. Dauplat J, Thivat E, Rouanet P, et al. STIC-RMI Working Group. Risk factors associated with complications after unilateral immediate breast reconstruction: a french prospective multicenter study. In Vivo 2021;35:937-45.

32. Leysen L, Beckwée D, Nijs J, et al. Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis. Support Care Cancer 2017;25:3607-43.

33. Humar P, Moroni E, Raghuram A, et al. Upper extremity functional outcomes after breast cancer treatment: an analysis of DASH score in breast reconstruction patients. Aesthet Surg J 2024;44:396-403.

34. Zehra S, Doyle F, Barry M, Walsh S, Kell MR. Health-related quality of life following breast reconstruction compared to total mastectomy and breast-conserving surgery among breast cancer survivors: a systematic review and meta-analysis. Breast Cancer 2020;27:534-66.

35. Penha TR, Botter B, Heuts EM, Voogd AC, von Meyenfeldt MF, van der Hulst RR. Quality of life in patients with breast cancer-related lymphedema and reconstructive breast surgery. J Reconstr Microsurg 2016;32:484-90.

36. Schubart JR, Emerich M, Farnan M, Stanley Smith J, Kauffman GL, Kass RB. Screening for psychological distress in surgical breast cancer patients. Ann Surg Oncol 2014;21:3348-53.

37. Mehnert A, Hartung TJ, Friedrich M, et al. One in two cancer patients is significantly distressed: prevalence and indicators of distress. Psychooncology 2018;27:75-82.

38. Hass HG, Seywald M, Wöckel A, Muco B, Tanriverdi M, Stepien J. Psychological distress in breast cancer patients during oncological inpatient rehabilitation: incidence, triggering factors and correlation with treatment-induced side effects. Arch Gynecol Obstet 2023;307:919-25.

39. Coriddi M, Kim LN, Haglich K, et al. The impact of lymphedema on patient-reported outcomes after breast reconstruction: a preliminary propensity score-matched analysis. Ann Surg Oncol 2023;30:3061-71.

40. Fu MR. Women at work with breast cancer-related lymphoedema. J Lymphoedema 2008;3:20-5.

41. Moffatt CJ, Franks PJ, Doherty DC, et al. Lymphoedema: an underestimated health problem. QJM 2003;96:731-8.

42. Shih YC, Xu Y, Cormier JN, et al. Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: a 2-year follow-up study. J Clin Oncol 2009;27:2007-14.

43. Vella F, Filetti V, Cirrincione L, et al. Work ability after breast cancer: study of healthcare personnel operating in a hospital of South Italy. Int J Environ Res Public Health 2022;19:10835.

44. Dean LT, Moss SL, Ransome Y, et al. "It still affects our economic situation": long-term economic burden of breast cancer and lymphedema. Support Care Cancer 2019;27:1697-708.

45. Pereira ACP, Koifman RJ, Bergmann A. Incidence and risk factors of lymphedema after breast cancer treatment: 10 years of follow-up. Breast 2017;36:67-73.

46. Liu YF, Liu JE, Mak YW, et al. Prevalence and predictors of breast cancer-related arm lymphedema over a 10-year period in postoperative breast cancer patients: a cross-sectional study. Eur J Oncol Nurs 2021;51:101909.

47. Mikami T, Koyama A, Hashimoto K, et al. Pathological changes in the lymphatic system of patients with secondary upper limb lymphoedema. Sci Rep 2019;9:8499.

48. Quartuccio N, Siracusa M, Pappalardo M, Arnone A, Arnone G. Sentinel node identification in melanoma: current clinical impact, new emerging SPECT radiotracers and technological advancements. an update of the last decade. Curr Radiopharm 2020;13:32-41.

49. Smoot BJ, Mastick J, Shepherd J, et al. Use of dual-energy X-ray absorptiometry to assess soft tissue composition in breast cancer survivors with and without lymphedema. Lymphat Res Biol 2022;20:391-7.

50. Johnson KC, DeSarno M, Ashikaga T, Dee J, Henry SM. Ultrasound and clinical measures for lymphedema. Lymphat Res Biol 2016;14:8-17.

51. Canales-Lachén E, Asunsolo Á, Manrique OJ, Blázquez J, Holguín P, Maldonado AA. The use of ultrasound imaging for upper extremity lymphedema after breast cancer: a systematic review. J Reconstr Microsurg 2023;39:102-10.

52. Thomis S, Devoogdt N, De Vrieze T, Bechter-Hugl B, Heroes AK, Fourneau I. Relation between early disturbance of lymphatic transport visualized with lymphofluoroscopy and other clinical assessment methods in patients with breast cancer. Clin Breast Cancer 2022;22:e37-47.

53. Armer JM, Stewart BR. A comparison of four diagnostic criteria for lymphedema in a post-breast cancer population. Lymphat Res Biol 2005;3:208-17.

54. Tierney S, Aslam M, Rennie K, Grace P. Infrared optoelectronic volumetry, the ideal way to measure limb volume. Eur J Vasc Endovasc Surg 1996;12:412-7.

55. Hayes S, Cornish B, Newman B. Comparison of methods to diagnose lymphoedema among breast cancer survivors: 6-month follow-up. Breast Cancer Res Treat 2005;89:221-6.

56. Cornish BH, Chapman M, Hirst C, Mirolo B, Bunce IH, Ward LC, Thomas BJ. Early diagnosis of lymphedema using multiple frequency bioimpedance. Lymphology 2001;34:2-11.

57. Vicini F, Shah C, Lyden M, Whitworth P. Bioelectrical impedance for detecting and monitoring patients for the development of upper limb lymphedema in the clinic. Clin Breast Cancer 2012;12:133-7.

58. Shah C, Vicini F, Beitsch P, et al. The use of bioimpedance spectroscopy to monitor therapeutic intervention in patients treated for breast cancer related lymphedema. Lymphology 2013;46:184-92.

59. Ward LC, Dylke E, Czerniec S, Isenring E, Kilbreath SL. Confirmation of the reference impedance ratios used for assessment of breast cancer-related lymphedema by bioelectrical impedance spectroscopy. Lymphat Res Biol 2011;9:47-51.

60. Czerniec SA, Ward LC, Lee MJ, Refshauge KM, Beith J, Kilbreath SL. Segmental measurement of breast cancer-related arm lymphoedema using perometry and bioimpedance spectroscopy. Support Care Cancer 2011;19:703-10.

61. Hayes S, Janda M, Cornish B, Battistutta D, Newman B. Lymphedema secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors. Lymphology 2008;41:18-28.

62. Pappalardo M, Starnoni M, Franceschini G, Baccarani A, De Santis G. Breast cancer-related lymphedema: recent updates on diagnosis, severity and available treatments. J Pers Med 2021;11:402.

63. de Sire A, Losco L, Cigna E, et al. Three-dimensional laser scanning as a reliable and reproducible diagnostic tool in breast cancer related lymphedema rehabilitation: a proof-of-principle study. Eur Rev Med Pharmacol Sci 2020;24:4476-85.

64. Aldrich MB, Rasmussen JC, Fife CE, Shaitelman SF, Sevick-Muraca EM. The development and treatment of lymphatic dysfunction in cancer patients and survivors. Cancers 2020;12:2280.

65. Seward C, Skolny M, Brunelle C, Asdourian M, Salama L, Taghian AG. A comprehensive review of bioimpedance spectroscopy as a diagnostic tool for the detection and measurement of breast cancer-related lymphedema. J Surg Oncol 2016;114:537-42.

66. Qin ES, Bowen MJ, Chen WF. Diagnostic accuracy of bioimpedance spectroscopy in patients with lymphedema: a retrospective cohort analysis. J Plast Reconstr Aesthet Surg 2018;71:1041-50.

67. Koehler LA, Mayrovitz HN. Spatial and temporal variability of upper extremity edema measures after breast cancer surgery. Lymphat Res Biol 2019;17:308-15.

68. Mayrovitz HN. Medical applications of skin tissue dielectric constant measurements. Cureus 2023;15:e50531.

69. Mayrovitz HN, Arzanova E, Somarriba S, Eisa S. Factors affecting interpretation of tissue dielectric constant (TDC) in assessing breast cancer treatment related lymphedema (BCRL). Lymphology 2019;52:92-102.

70. Polat AK, Karabacak U, Mutlu V, Tomak L, Bilgici A. Early diagnosis of lymphedema after breast cancer treatment: bio-impedance spectroscopy. J Breast Health 2017;13:83-7.

71. Watanabe S, Kajita H, Suzuki Y, et al. Photoacoustic lymphangiography is a possible alternative for lymphedema staging. J Vasc Surg Venous Lymphat Disord 2022;10:1318-24.e2.

72. Zackrisson S, van de Ven SMWY, Gambhir SS. Light in and sound out: emerging translational strategies for photoacoustic imaging. Cancer Res 2014;74:979-1004.

73. O'Toole J, Jammallo LS, Miller CL, Skolny MN, Specht MC, Taghian AG. Screening for breast cancer-related lymphedema: the need for standardization. Oncologist 2013;18:350-2.

74. Figueroa BA, Lammers JD, Al-malak M, Pandey S, Chen WF. Lymphoscintigraphy versus indocyanine green lymphography-which should be the gold standard for lymphedema imaging? Lymphatics 2023;1:25-33.

75. Sun F, Skolny MN, Swaroop MN, et al. The need for preoperative baseline arm measurement to accurately quantify breast cancer-related lymphedema. Breast Cancer Res Treat 2016;157:229-40.

76. Executive Committee. The diagnosis and treatment of peripheral lymphedema: 2016 consensus document of the international society of lymphology. Lymphology 2016;49:170-84.

77. Executive Committee of the International Society of Lymphology.. The diagnosis and treatment of peripheral lymphedema: 2020 consensus document of the international society of lymphology. Lymphology 2020;53:3-19.

78. International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 consensus document of the international society of lymphology. Lymphology 2013;46:1-11.

79. Halsted WS. The results of operations for the cure of cancer of the breast performed at the johns Hopkins hospital from June, 1889, to January, 1894. Ann Surg 1894;20:497-555.

80. Christiansen P, Mele M, Bodilsen A, Rocco N, Zachariae R. Breast-conserving surgery or mastectomy? Impact on survival. Ann Surg Open 2022;3:e205.

81. Abass MO, Gismalla MDA, Alsheikh AA, Elhassan MMA. Axillary lymph node dissection for breast cancer: efficacy and complication in developing countries. J Glob Oncol 2018;4:1-8.

82. Tfayli A, Temraz S, Abou Mrad R, Shamseddine A. Breast cancer in low- and middle-income countries: an emerging and challenging epidemic. J Oncol 2010;2010:490631.

83. Boyages J, Vicini FA, Manavi BA, et al. Axillary treatment and chronic breast cancer-related lymphedema: implications for prospective surveillance and intervention from a randomized controlled trial. JCO Oncol Pract 2023;19:1116-24.

84. Basta MN, Wu LC, Kanchwala SK, et al. Reliable prediction of postmastectomy lymphedema: the risk assessment tool evaluating lymphedema. Am J Surg 2017;213:1125-33.e1.

85. Coriddi M, Khansa I, Stephens J, Miller M, Boehmler J, Tiwari P. Analysis of factors contributing to severity of breast cancer-related lymphedema. Ann Plast Surg 2015;74:22-5.

86. Lee J, Jung JH, Kim WW, et al. Ten-year oncologic outcomes in T1-3N1 breast cancer after targeted axillary sampling: a retrospective study. Ann Surg Oncol 2023;30:4669-77.

87. Miller CL, Specht MC, Skolny MN, et al. Risk of lymphedema after mastectomy: potential benefit of applying ACOSOG Z0011 protocol to mastectomy patients. Breast Cancer Res Treat 2014;144:71-7.

88. Afif M, Kouhen F, Benjaafar N. Hypofractionated radiation therapy in the management of breast cancer: analysis of 350 patients treated in the national institute of oncology of Rabat, Morocco. Tumori 2019;105:4-5.

89. Bellefqih S, Elmajjaoui S, Aarab J, et al. Hypofractionated regional nodal irradiation for women with node-positive breast cancer. Int J Radiat Oncol Biol Phys 2017;97:563-70.

90. Chaffai I, Cao K, Kissel M, et al. [Patient selection and early tolerance of whole breast irradiation according to the "fast forward" protocol: preliminary results]. Cancer Radiother 2022;26:542-6.

91. Coen JJ, Taghian AG, Kachnic LA, Assaad SI, Powell SN. Risk of lymphedema after regional nodal irradiation with breast conservation therapy. Int J Radiat Oncol Biol Phys 2003;55:1209-15.

92. De Matteis S, Facondo G, Valeriani M, et al. Hypofractionated radiation therapy (HFRT) of breast/chest wall and regional nodes in locally advanced breast cancer: toxicity profile and survival outcomes in retrospective monoistitutional study. Clin Breast Cancer 2022;22:e332-40.

93. Doss V, Healy E, Beyer S, Jhawar SR, Bazan JG, White J. Abstract P3-19-17: Radiation of the low axilla in the prone position. Cancer Res 2022; 82 (4_Supplement):P3-19.

94. Gil GOB, de Andrade WP, Diniz PHC, et al. A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis. Front Oncol 2023;13:1202544.

95. Kanda MH, da Costa Vieira RA, Lima JPSN, Paiva CE, de Araujo RLC. Late locoregional complications associated with adjuvant radiotherapy in the treatment of breast cancer: systematic review and meta-analysis. J Surg Oncol 2020;121:766-76.

96. Heiman AJ, Gabbireddy SR, Kotamarti VS, Ricci JA. A meta-analysis of autologous microsurgical breast reconstruction and timing of adjuvant radiation therapy. J Reconstr Microsurg 2021;37:336-45.

97. Naoum GE, Salama L, Niemierko A, et al. Single stage direct-to-implant breast reconstruction has lower complication rates than tissue expander and implant and comparable rates to autologous reconstruction in patients receiving postmastectomy radiation. Int J Radiat Oncol Biol Phys 2020;106:514-24.

98. Lauritzen E, Damsgaard TE. Use of indocyanine green angiography decreases the risk of complications in autologous- and implant-based breast reconstruction: a systematic review and meta-analysis. J Plast Reconstr Aesthet Surg 2021;74:1703-17.

99. Murphy JA, Milner TD, O'Donoghue JM. Contralateral risk-reducing mastectomy in sporadic breast cancer. Lancet Oncol 2013;14:e262-9.

100. Yang RL, Newman AS, Lin IC, et al. Trends in immediate breast reconstruction across insurance groups after enactment of breast cancer legislation. Cancer 2013;119:2462-8.

101. Xie Y, Tang Y, Wehby GL. Federal health coverage mandates and health care utilization: the case of the women's health and cancer rights act and use of breast reconstruction surgery. J Womens Health 2015;24:655-62.

102. Fijany AJ, Friedlich N, Olsson SE, Bishay AE, Pekarev M. Current trends in autologous breast reconstruction and the implications of impending changes to insurance reimbursement. Cureus 2023;15:e43855.

103. Song WJ, Kang SG, Kim EK, et al. Current status of and trends in post-mastectomy breast reconstruction in Korea. Arch Plast Surg 2020;47:118-25.

104. Ho D, Chan E, Izwan S, et al. Uptake of breast reconstruction following mastectomy: a gold coast experience. ANZ J Surg 2022;92:3011-6.

105. Unukovych D, Gümüscü R, Wärnberg F, et al. Breast reconstruction patterns from a Swedish nation-wide survey. Eur J Surg Oncol 2020;46:1867-73.

106. Bodilsen A, Christensen S, Christiansen P, Damsgaard TE, Zachariae R, Jensen AB. Socio-demographic, clinical, and health-related factors associated with breast reconstruction - a nationwide cohort study. Breast 2015;24:560-7.

107. Al-Ghazal SK, Sully L, Fallowfield L, Blamey RW. The psychological impact of immediate rather than delayed breast reconstruction. Eur J Surg Oncol 2000;26:17-9.

108. Wellisch DK, Schain WS, Noone RB, Little JW 3rd. Psychosocial correlates of immediate versus delayed reconstruction of the breast. Plast Reconstr Surg 1985;76:713-8.

109. Stevens LA, McGrath MH, Druss RG, Kister SJ, Gump FE, Forde KA. The psychological impact of immediate breast reconstruction for women with early breast cancer. Plast Reconstr Surg 1984;73:619-28.

110. Elkowitz A, Colen S, Slavin S, Seibert J, Weinstein M, Shaw W. Various methods of breast reconstruction after mastectomy: an economic comparison. Plast Reconstr Surg 1993;92:77-83.

111. Al-Ghazal SK, Fallowfield L, Blamey RW. Comparison of psychological aspects and patient satisfaction following breast conserving surgery, simple mastectomy and breast reconstruction. Eur J Cancer 2000;36:1938-43.

112. Khoo A, Kroll SS, Reece GP, et al. A comparison of resource costs of immediate and delayed breast reconstruction. Plast Reconstr Surg 1998;101:964-8; discussion 969.

113. Alderman AK, Wilkins EG, Kim HM, Lowery JC. Complications in postmastectomy breast reconstruction: two-year results of the Michigan breast reconstruction outcome study. Plast Reconstr Surg 2002;109:2265-74.

114. Saheb-Al-Zamani M, Cordeiro E, O'Neill AC, Hofer SOP, Cil TD, Zhong T. Early postoperative complications from national surgical quality improvement program: a closer examination of timing and technique of breast reconstruction. Ann Plast Surg 2021;86:S159-64.

115. Prantl L, Moellhoff N, von Fritschen U, et al. Immediate versus secondary DIEP flap breast reconstruction: a multicenter outcome study. Arch Gynecol Obstet 2020;302:1451-9.

116. Juhl AA, Christensen S, Zachariae R, Damsgaard TE. Unilateral breast reconstruction after mastectomy - patient satisfaction, aesthetic outcome and quality of life. Acta Oncol 2017;56:225-31.

117. Matar DY, Wu M, Haug V, Orgill DP, Panayi AC. Surgical complications in immediate and delayed breast reconstruction: a systematic review and meta-analysis. J Plast Reconstr Aesthet Surg 2022;75:4085-95.

118. Kuhlefelt C, Repo JP, Jahkola T, Kauhanen S, Homsy P. Immediate versus delayed breast reconstruction: long-term follow-up on health-related quality of life and satisfaction with breasts. J Plast Reconstr Aesthet Surg 2024;88:478-86.

119. Srinivasa DR, Garvey PB, Qi J, et al. Direct-to-implant versus two-stage tissue expander/implant reconstruction: 2-year risks and patient-reported outcomes from a prospective, multicenter study. Plast Reconstr Surg 2017;140:869-77.

120. Jonczyk MM, Jean J, Graham R, Chatterjee A. Surgical trends in breast cancer: a rise in novel operative treatment options over a 12 year analysis. Breast Cancer Res Treat 2019;173:267-74.

121. Quinn TT, Miller GS, Rostek M, Cabalag MS, Rozen WM, Hunter-Smith DJ. Prosthetic breast reconstruction: indications and update. Gland Surg 2016;5:174-86.

122. Svee A, Falk-Delgado A, Folkvaljon F, et al. Use of the cephalic vein in DIEP breast reconstruction does not increase risk of lymphedema of the ipsilateral arm. Plast Reconstr Surg 2023;151:195-201.

123. King ICC, Mellington AJ, Jones ME, Hazari A. Cephalic vein transposition in autologous breast reconstruction salvage: a review of outcomes and implications for patient care. Eur J Plast Surg 2018;41:671-6.

124. Siotos C, Sebai ME, Wan EL, et al. Breast reconstruction and risk of arm lymphedema development: a meta-analysis. J Plast Reconstr Aesthet Surg 2018;71:807-18.

125. Almailabi M, Daghistani M, Khan M. A comparison of developing breast cancer-related lymphedema between mastectomy with reconstruction and mastectomy alone among breast cancer patients in Saudi Arabia. Available from: https://journals.lww.com/sasj/fulltext/2019/07040/a_comparison_of_developing_breast_cancer_related.6.aspx [Last accessed on 14 Jun 2024].

126. Jeon HB, Jung JH, Im SH, et al. Association between immediate breast reconstruction and the development of breast cancer-related lymphedema. Plast Reconstr Surg 2023;151:214e-22e.

127. Taghioff SM, Slavin BR, Mehra S, et al. Post-mastectomy lymphedema in breast reconstruction: a multicenter 10-year temporal stratification. Plast Reconstr Surg 2022;10:5-6.

128. Clegg DJ, Whiteaker EN, Salomon BJ, et al. The development of breast cancer-related lymphedema after mastectomy in a rural population. Am Surg 2023;89:3591-3.

129. Park JH, Merriman J, Brody A, et al. Limb volume changes and activities of daily living: a prospective study. Lymphat Res Biol 2021;19:261-8.

130. Lee KT, Kim J, Jeon BJ, et al. Association of the breast reconstruction modality with the development of postmastectomy lymphedema: a long-term follow-up study. Eur J Surg Oncol 2023;49:1177-83.

131. Slavin BR, Taghioff SM, Mehra S, et al. P58. risk of post mastectomy lymphedema in autologous breast reconstruction: a multi-center 10-year analysis of 9,660 patients stratified by flap-type and timing of reconstruction. Plast Reconstr Surg 2022;10:76-7.

132. Zhang X, He X, Tang B, et al. Risk factors of lymphedema on affected side of upper limb after breast cancer surgery - report from a single center of China. Available from: http://www.ijcem.com/files/ijcem0040612.pdf [Last accessed on 11 May 2024].

133. Byun HK, Chang JS, Im SH, et al. Risk of lymphedema following contemporary treatment for breast cancer: an analysis of 7617 consecutive patients from a multidisciplinary perspective. Ann Surg 2021;274:170-8.

134. Lauritzen E, Bredgaard R, Bonde C, Jensen LT, Tvedskov T, Damsgaard TE. Indocyanine green angiography for autologous breast reconstruction: a prospective observational study. Ann Breast Surg 2023:8.

135. Laws A, Lagendijk M, Grossmith S, et al. Long-term patient-reported arm symptoms in breast cancer survivors. Ann Surg Oncol 2024;31:1623-33.

136. Aoishi Y, Oura S, Nishiguchi H, et al. Risk factors for breast cancer-related lymphedema: correlation with docetaxel administration. Breast Cancer 2020;27:929-37.

137. Fisher C, Jackson M, Ridings J, et al. Prospective phase II clinical trial of hypofractionated radiation in breast cancer patients undergoing comprehensive nodal irradiation for node positive disease. Int J Radiat Oncol 2019;105:S41-2.

138. Tan S, Pan L, Zhao H, Hu J, Chen H. Perioperative nursing for immediate breast reconstruction with deep inferior epigastric perforator flap after breast cancer resection. J Thorac Dis 2018;10:4017-22.

139. Wong CJ, Tay MRJ, Aw HZ. Prevalence and risk factors of adhesive capsulitis in asian breast cancer patients undergoing an outpatient community cancer rehabilitation program. Arch Phys Med Rehabil 2021;102:843-8.

140. Asdourian MS, Swaroop MN, Sayegh HE, et al. Association between precautionary behaviors and breast cancer-related lymphedema in patients undergoing bilateral surgery. J Clin Oncol 2017;35:3934-41.

141. Lauritzen E, Bredgaard R, Laustsen-Kiel CM, Hansen L, Tvedskov T, Damsgaard TE. Indocyanine green angiography in oncoplastic breast surgery, a prospective study. J Plast Reconstr Aesthet Surg 2023;85:276-86.

142. Alba B, Schultz B, Qin LA, et al. Postoperative upper extremity function in implant and autologous breast reconstruction. J Reconstr Microsurg 2020;36:151-6.

143. Zang H, Bi Y, Mu L. [Progress of treatment and prevention of breast cancer related lymphedema]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2016;30:1567-70.

144. Lee KT, Bang SI, Pyon JK, Hwang JH, Mun GH. Method of breast reconstruction and the development of lymphoedema. Br J Surg 2017;104:230-7.

145. Gergich NL, Pfalzer LA, McGarvey C, Springer B, Gerber LH, Soballe P. Preoperative assessment enables the early diagnosis and successful treatment of lymphedema. Cancer 2008;112:2809-19.

146. Rafn BS, Bodilsen A, von Heymann A, et al. Examining the efficacy of treatments for arm lymphedema in breast cancer survivors: an overview of systematic reviews with meta-analyses. EClinicalMedicine 2024;67:102397.

147. De Vrieze T, Gebruers N, Nevelsteen I, et al. Manual lymphatic drainage with or without fluoroscopy guidance did not substantially improve the effect of decongestive lymphatic therapy in people with breast cancer-related lymphoedema (EFforT-BCRL trial): a multicentre randomised trial. J Physiother 2022;68:110-22.

148. De Vrieze T, Gebruers N, Nevelsteen I, et al. Does manual lymphatic drainage add value in reducing suprafascial fluid accumulation and skin elasticity in patients with breast cancer-related lymphedema? Phys Ther 2022;102:pzac137.

149. Marotta N, Lippi L, Ammendolia V, et al. Efficacy of kinesio taping on upper limb volume reduction in patients with breast cancer-related lymphedema: a systematic review of randomized controlled trials. Eur J Phys Rehabil Med 2023;59:237-47.

150. Hayes SC, Singh B, Reul-Hirche H, et al. The effect of exercise for the prevention and treatment of cancer-related lymphedema: a systematic review with meta-analysis. Med Sci Sports Exerc 2022;54:1389-99.

151. Shao Y, Zhong DS. Manual lymphatic drainage for breast cancer-related lymphoedema. Eur J Cancer Care 2017;26:e12517.

152. McNeely ML, Peddle CJ, Yurick JL, Dayes IS, Mackey JR. Conservative and dietary interventions for cancer-related lymphedema: a systematic review and meta-analysis. Cancer 2011;117:1136-48.

153. Rangon FB, da Silva J, Dibai-Filho AV, Guirro RRJ, Guirro ECO. Effects of complex physical therapy and multimodal approaches on lymphedema secondary to breast cancer: a systematic review and meta-analysis of randomized controlled trials. Arch Phys Med Rehabil 2022;103:353-63.

154. Rogan S, Taeymans J, Luginbuehl H, Aebi M, Mahnig S, Gebruers N. Therapy modalities to reduce lymphoedema in female breast cancer patients: a systematic review and meta-analysis. Breast Cancer Res Treat 2016;159:1-14.

155. Smoot B, Chiavola-Larson L, Lee J, Manibusan H, Allen DD. Effect of low-level laser therapy on pain and swelling in women with breast cancer-related lymphedema: a systematic review and meta-analysis. J Cancer Surviv 2015;9:287-304.

156. Ezzo J, Manheimer E, McNeely ML, et al. Manual lymphatic drainage for lymphedema following breast cancer treatment. Cochrane Database Syst Rev 2015;2015:CD003475.

157. Qiao J, Yang LN, Kong YH, Huang X, Li Y, Bai DQ. Effect of manual lymphatic drainage on breast cancer-related postmastectomy lymphedema: a meta-analysis of randomized controlled trials. Cancer Nurs 2023;46:159-66.

158. Chen HY, Tsai HH, Tam KW, Huang TW. Effects of photobiomodualtion therapy on breast cancer-related lymphoedema: a systematic review and meta-analysis of randomised controlled trials. Complement Ther Med 2019;47:102200.

159. Gatt M, Willis S, Leuschner S. A meta-analysis of the effectiveness and safety of kinesiology taping in the management of cancer-related lymphoedema. Eur J Cancer Care 2017;26:e12510.

160. Yeung W, Semciw AI. Aquatic therapy for people with lymphedema: a systematic review and meta-analysis. Lymphat Res Biol 2018;16:9-19.

161. Shamoun S, Ahmad M. Complete decongestive therapy effect on breast cancer related to lymphedema: a systemic review and meta-analysis of randomized controlled trials. Asian Pac J Cancer Prev 2023;24:2225-38.

162. O'Brien BM, Sykes P, Threlfall GN, Browning FS. Microlymphaticovenous anastomoses for obstructive lymphedema. Plast Reconstr Surg 1977;60:197-211.

163. Gennaro P, Gabriele G, Mihara M, et al. Supramicrosurgical lymphatico-venular anastomosis (LVA) in treating lymphoedema: 36-months preliminary report. Eur Rev Med Pharmacol Sci 2016;20:4642-53.

164. Kim HO, Woo KJ, Kim BS, Kang SY, Moon BS, Yoon HJ. Lymphoscintigraphic findings as indicators of lymphaticovenous anastomosis outcome in patients with extremity lymphedema: a retrospective cohort study. Clin Nucl Med 2021;46:549-55.

165. Khan AA, Hernan I, Adamthwaite JA, Ramsey KWD. Feasibility study of combined dynamic imaging and lymphaticovenous anastomosis surgery for breast cancer-related lymphoedema. Br J Surg 2019;106:100-10.

166. Damstra RJ, Voesten HG, van Schelven WD, van der Lei B. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 2009;113:199-206.

167. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: a prospective study. Plast Reconstr Surg 2010;126:752-8.

168. Weiss M, Baumeister RG, Frick A, Wallmichrath J, Bartenstein P, Rominger A. Lymphedema of the upper limb: evaluation of the functional outcome by dynamic imaging of lymph kinetics after autologous lymph vessel transplantation. Clin Nucl Med 2015;40:e117-23.

169. Meuli JN, Guiotto M, Elmers J, Mazzolai L, di Summa PG. Outcomes after microsurgical treatment of lymphedema: a systematic review and meta-analysis. Int J Surg 2023;109:1360-72.

170. Deban M, McKinnon JG, Temple-Oberle C. Mitigating breast-cancer-related lymphedema-a calgary program for immediate lymphatic reconstruction (ILR). Curr Oncol 2023;30:1546-59.

171. Boccardo F, Casabona F, De Cian F, et al. Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: over 4 years follow-up. Microsurgery 2014;34:421-4.

172. Feldman S, Bansil H, Ascherman J, et al. Single Institution experience with lymphatic microsurgical preventive healing approach (LYMPHA) for the primary prevention of lymphedema. Ann Surg Oncol 2015;22:3296-301.

173. Wainwright D, Weinstein B, Le NK, Parikh J, Panetta NJ. Reliable location of upper extremity lymphatic channels for use in immediate lymphatic reconstruction. Ann Plast Surg 2023;90:S391-4.

174. Le NK, Weinstein B, Serraneau K, Tavares T, Laronga C, Panetta N. The learning curve: trends in the first 100 immediate lymphatic reconstructions performed at a single institution. Ann Plast Surg 2021;86:S495-7.

175. Schwarz GS, Grobmyer SR, Djohan RS, et al. Axillary reverse mapping and lymphaticovenous bypass: lymphedema prevention through enhanced lymphatic visualization and restoration of flow. J Surg Oncol 2019;120:160-7.

176. Johnson AR, Fleishman A, Tran BNN, et al. Developing a lymphatic surgery program: a first-year review. Plast Reconstr Surg 2019;144:975e-85e.

177. Jørgensen MG, Toyserkani NM, Sørensen JA. The effect of prophylactic lymphovenous anastomosis and shunts for preventing cancer-related lymphedema: a systematic review and meta-analysis. Microsurgery 2018;38:576-85.

178. Levy AS, Murphy AI, Ishtihar S, et al. Lymphatic microsurgical preventive healing approach for the primary prevention of lymphedema: a 4-year follow-up. Plast Reconstr Surg 2023;151:413-20.

179. Clodius L, Smith PJ, Bruna J, Serafin D. The lymphatics of the groin flap. Ann Plast Surg 1982;9:447-58.

180. Becker C, Assouad J, Riquet M, Hidden G. Postmastectomy lymphedema: long-term results following microsurgical lymph node transplantation. Ann Surg 2006;243:313-5.

181. Nakajima E, Nakajima R, Tsukamoto S, Koide Y, Yarita T, Kato H. Omental transposition for lymphedema after a breast cancer resection: report of a case. Surg Today 2006;36:175-9.

182. Jarvis NR, Torres RA, Avila FR, Forte AJ, Rebecca AM, Teven CM. Vascularized omental lymphatic transplant for upper extremity lymphedema: A systematic review. Cancer Rep 2021;4:e1370.

183. Skladman R, Moritz WR, Tenenbaum EJ, Christensen JM, Sacks JM. Vascularized omental tissue transfer for the treatment of lymphedema: a review. Plast Aesthet Res 2023;10:66.

184. Vignes S, Blanchard M, Yannoutsos A, Arrault M. Complications of autologous lymph-node transplantation for limb lymphoedema. Eur J Vasc Endovasc Surg 2013;45:516-20.

185. Pons G, Masia J, Loschi P, Nardulli ML, Duch J. A case of donor-site lymphoedema after lymph node-superficial circumflex iliac artery perforator flap transfer. J Plast Reconstr Aesthet Surg 2014;67:119-23.

186. Teven CM, Yi J, Hammond JB, et al. Expanding the horizon: single-port robotic vascularized omentum lymphatic transplant. Plast Reconstr Surg Glob Open 2021;9:e3414.

187. Shimbo K, Kawamoto H, Koshima I. Comparative study of conservative treatment and lymphaticovenular anastomosis with compression therapy for early-stage breast cancer-related lymphoedema. J Plast Reconstr Aesthet Surg 2024;88:390-6.

188. Ciudad P, Bolletta A, Kaciulyte J, et al. The breast cancer-related lymphedema multidisciplinary approach: Algorithm for conservative and multimodal surgical treatment. Microsurgery 2023;43:427-36.

189. Brorson H, Svensson H. Complete reduction of lymphoedema of the arm by liposuction after breast cancer. Scand J Plast Reconstr Surg Hand Surg 1997;31:137-43.

190. Damstra RJ, Voesten HG, Klinkert P, Brorson H. Circumferential suction-assisted lipectomy for lymphoedema after surgery for breast cancer. Br J Surg 2009;96:859-64.

191. Chiang SN, Skolnick GB, Sacks JM, Christensen JM. Complication profile of combined microvascular breast reconstruction combined with vascularised lymph node transplant. Available from: https://profiles.wustl.edu/en/publications/complication-profile-of-combined-microvascular-breast-reconstruct [Last accessed on 22 May 2024].

192. Chang EI, Ibrahim A, Liu J, et al. Optimizing quality of life for patients with breast cancer-related lymphedema: a prospective study combining DIEP flap breast reconstruction and lymphedema surgery. Plast Reconstr Surg 2020;145:676e-85e.

193. Hamdi M, Ramaut L, De Baerdemaeker R, Zeltzer A. Decreasing donor site morbidity after groin vascularized lymph node transfer with lessons learned from a 12-year experience and review of the literature. J Plast Reconstr Aesthet Surg 2021;74:540-8.

194. Di Taranto G, Coleman GJ, Hardwicke J, Wallis KL, Skillman J. A comparative study between deep inferior epigastric artery perforator flap breast reconstruction and DIEP flap breast reconstruction coupled with vascularized lymph node transfer: improving the quality of life of patients with breast cancer related lymphedema without affecting donor site outcomes. Microsurgery 2023;43:213-21.

195. Ozmen BB, Schwarz G. Predicting breast cancer related lymphedema after immediate lymphatic reconstruction: an artificial intelligence approach with synthetic data. Prs-Glob Open 2024;12:65.

Cite This Article

Export citation file: BibTeX | RIS

OAE Style

Laustsen-Kiel CM, Hansen L, Lauritzen E, Damsgaard TE. Breast reconstruction and breast cancer-related lymphedema: insights and perspectives. Plast Aesthet Res 2024;11:17. http://dx.doi.org/10.20517/2347-9264.2024.32

AMA Style

Laustsen-Kiel CM, Hansen L, Lauritzen E, Damsgaard TE. Breast reconstruction and breast cancer-related lymphedema: insights and perspectives. Plastic and Aesthetic Research. 2024; 11: 17. http://dx.doi.org/10.20517/2347-9264.2024.32

Chicago/Turabian Style

Cecilie Mullerup Laustsen-Kiel, Laura Hansen, Elisabeth Lauritzen, Tine Engberg Damsgaard. 2024. "Breast reconstruction and breast cancer-related lymphedema: insights and perspectives" Plastic and Aesthetic Research. 11: 17. http://dx.doi.org/10.20517/2347-9264.2024.32

ACS Style

Laustsen-Kiel, CM.; Hansen L.; Lauritzen E.; Damsgaard TE. Breast reconstruction and breast cancer-related lymphedema: insights and perspectives. Plast. Aesthet. Res. 2024, 11, 17. http://dx.doi.org/10.20517/2347-9264.2024.32

About This Article

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Data & Comments

Data

Views
150
Downloads
19
Citations
0
Comments
0
2

Comments

Comments must be written in English. Spam, offensive content, impersonation, and private information will not be permitted. If any comment is reported and identified as inappropriate content by OAE staff, the comment will be removed without notice. If you have any queries or need any help, please contact us at support@oaepublish.com.

0
Download PDF
Cite This Article 1 clicks
Like This Article 2 likes
Share This Article
Scan the QR code for reading!
See Updates
Contents
Figures
Related
Plastic and Aesthetic Research
ISSN 2349-6150 (Online)   2347-9264 (Print)

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/