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    Diagnosis and Treatment of Axillary Web Syndrome:An Overview

    2020-12-12 13:31:35ElanYANGXiongweiLIXiaoLONG

    Elan YANG ,Xiongwei LI ,Xiao LONG

    1 Department of Plastic Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

    SUMMARY Axillary web syndrome (AWS) is a self-limiting disease that can occur as an early or possibly late postoperative complication post-axillary surgery.This syndrome is characterized by the spread of the cords of subcutaneous tissue extending from the axilla into the arm and is clinically associated with pain and limited movement of the shoulder in the affected limb.Although its pathophysiology is not well established,the most common cause is surgery-related axillary lymphatic injury.Both the echography and magnetic resonance imaging results support the lymphatic hypothesis.The diagnosis of AWS is based on physical examination.Risk factors may include extensiveness of surgery,younger age,hypertension,lower body mass index,ethnicity,and healing complications.Effective clinical intervention shortens the natural course of AWS and improves the quality of life of patients with AWS.Treatments may include physical therapy,drug therapy,manual drainage,instrument-assisted soft tissue mobilization (IASTM),thoracic manipulation and stretching,manual axial distraction,percutaneous needle cord disruption with fat grafting and Xiaflex injection,and surgical intervention.Routine surgical treatment for AWS may not be recommended.Further research is needed to provide more comprehensive improvements in the diagnosis and treatment of AWS.

    KEY WORDS Axillary web syndrome; Breast cancer; Axillary lymph node dissection; Sentinel lymph node biopsy

    INTRODUCTION

    Breast cancer is the second most common cancer among all types of malignancies and is the most frequently occurring cancer in women.[1-3]At present,surgery is the most effective treatment for breast cancer.[4]With technological improvements in the diagnosis and treatment,along with better understanding of breast cancer,sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) have become two of the most common treatment methods for breast cancer.The use of these techniques has greatly improved the postoperative survival rate,and more attention is now focused on early postoperative recovery and improving the quality of life postoperatively.[4-5]However,postoperative complications of restriction in the shoulder function,edema,pain,and depression are increasing.[5]

    Axillary web syndrome (AWS) is one of the most common complications of axilla surgery.AWS appears as a visible web of axillary skin overlying palpable cords of tissue or string-like bands on the affected limb or chest; these cords or bands can be taut and painful during shoulder abduction.This syndrome most often occurs 5 to 12 weeks[6-11]after ALND or SLNB,although it may also occur 3 months postoperatively.[3,11-12]Clinicians do not fully understand the cord structures and have yet to reach a consensus on the diagnosis and treatment of AWS.Therefore,the ability to provide a reasonable treatment strategy to reduce the physical and psychological effects is still limited.The quality of life can be greatly affected,especially in patients who have received both SLNB and ALND.[13]The current diagnostic tools,such as biopsy,ultrasound,and magnetic resonance imaging,have assisted clinicians to diagnose and assess AWS.This review focuses on the current state of research on AWS.

    PAPER SELECTION

    The purpose of this study was to summarize the current literature on the etiology,epidemiology,pathophysiology,diagnosis,and treatment modalities of AWS.The selection criteria included papers that discussed the diagnosis and treatment protocols used for AWS after SLNB and ALND in patients who suffered from breast cancer.These searches were performed in the PubMed,Science Direct,and Google Scholar databases using the keywords AWS,breast cancer,and ALND.There were 11,24,and 328 relevant studies from PubMed,Science Direct,and Google Scholar.The most updated findings were summarized from 51 of these articles.

    EPIDEMIOLOGY

    Moskovitz et al.[11]retrospectively analyzed the data for 750 patients who received ALND from 1980 to 1996 and found that 44 patients had developed axillary nodules along with limited limb movement especially in shoulder abduction 1-8 weeks postoperatively.This syndrome was named AWS,and a 6% incidence rate was reported.At the same time,Leidenius et al.[14]performed a prospective study of 85 breast cancer patients and found that 26 of the 36 patients with ALND developed axillary nodules combined with a limited range of motion in the affected limb.The symptoms of these patients were consistent with AWS,and their incidence rate was as high as 72%.Bergmann et al.[12]evaluated 196 breast cancer patients in Brazil preoperatively to predict the overall survival rate postoperatively.They found that 0.6% of the patients had preoperative symptoms consistent with AWS,which indicated that some breast cancer patients might exhibit AWS preoperatively.In another study,Bergmann et al.[1]studied 193 breast cancer patients prospectively and reported that 28.1% of patients developed AWS 45 days postoperatively.They found that the incidence of AWS was 36% in patients who received ALND and 11.7% in those who received SLNB.

    Torres Lacomba et al.[7]conducted a prospective study on all breast cancer patients treated at Prince Asturias Hospital in Spain from 2005 to 2007 and included 116 breast cancer patients who underwent ALND surgery.Physical examination of patients who were suspected of presenting with AWS,56 patients were diagnosed with AWS,which gave an incidence rate of 48.3%.Nevola Teixeira et al.[8]reviewed the records of 108 patients from the European Cancer Center who had undergone ALND or SLNB from October 2012 to December 2012.After 20 patients,who were unwilling to participate in the study,were excluded,the average incidence of postoperative AWS in 88 patients with breast cancer was 36%.Koehler et al.[15]followed-up 36 patients with breast cancer who received ALND or SLNB for 3 months postoperatively.According to the clinical manifestations,AWS could be diagnosed in 17 patients,and the symptoms remained in 10 patients after 12 weeks; the overall AWS incidence rate was 47.2%.

    Schuitevoerder et al.[16]retrospectively studied melanoma patients who had received simple axillary SLNB from 2001 to 2015.According to the diagnostic criteria of AWS,21 of 465 patients presented with symptoms consistent with the diagnosis,which gave a 4.5% AWS incidence rate.Although the AWS incidence rate is lower post-simple axillary SLNB than that postoperatively in breast cancer patients,the incidence rate of AWS post-axillary SLNB was still higher than that for other complications,such as infections (3%),bleeding (1.5%),unhealed surgical site (0.8%),lymphangioma (5%),and lymphedema (0.4%).These findings act as a reminder for clinicians to inform melanoma patients of the possibility of AWS before undergoing SLNB.

    A recent study done by Figueira et al.[17]demonstrated that the majority of the cords appeared on the seventh day(66.1%) and the total incidence of the cords was 90.9%on the 180th day.In 80% of the AWS cases,the axilla is affected and >70% of the cords were palpable.Flexion and abduction of the shoulder showed reduced range of motion.Pain was present in 39.7% of the patients.

    ETIOLOGY

    Although ALND or SLNB is the most common treatment for breast cancer patients,axillary surgery can lead to some related complications,and AWS is a common early and possibly late postoperative complication.[17]The currently accepted pathogenesis of AWS involves surgery-induced injury of lymphatic vessels,[4]the most common causes of which are ALND and SLNB.[7,11,18]Other cancers,such as melanoma[9,16,18]and axillary furuncle[3],can lead to AWS.The common risk factors are as follows.

    Scope of Surgery

    The AWS occurrence rate increases as the scope of surgery increases.The incidence of AWS is significantly lower post-axillary lymph node biopsy than that post-ALND.[16]The incidence of AWS post-axillary lymph node biopsy in melanoma patients (4.5%) is significantly lower than that post-SLNB/ALND in breast cancer patients (28.1-72%).Schuitevoerder et al.[16]suggested that this may be related to other injuries caused by breast cancer surgery,postoperative infection,or lymphatic injury.The AWS incidence rate increases with an increase in the number of biopsied axillary lymph nodes.However,Fukushima et al.[4]studied 97 patients with breast cancer treated with lymph node excision and found that the average number of lymphadenectomies did not differ between the patients with and without AWS (12±1 and 12±2,respectively).

    Body mass index (BMI)

    The incidence of AWS is significantly higher in patients with a low BMI than that in those with a higher BMI.[7,11,15,19]The incidence of AWS post-SLNB or ALND was 15-33% lower in patients with a BMI > 25 kg/m2than in those with a BMI < 25 kg/m2.However,the relationship between BMI and AWS is unclear.[1]Torres Lacomba et al.[7]believe that obese patients have more lipid membranes in their limbs,which can delay the impact of the lymphatic vessels and prevent their infection,reduce the accumulation of lymphatic fluid,and hence,reduce the risk of AWS.Leidenius et al.[14]noted that the nodules of AWS are located under the skin,and therefore,it is easier to find nodules on thinner patients.Conversely,Fukushima et al.[4]reported average BMI value of 27.29±1.05 kg/m2in patients with AWS and 28.05 ± 0.98 kg/m2in those without AWS.The difference of BMI between the two groups was not significant.

    Age

    The incidence of early postoperative AWS is higher in younger than in older women postoperatively.[1,19-20]The incidence of postoperative AWS is 42% higher in women younger than 60 years of age compared to those older than that.[1]Torres Lacomba et al.reported an average age of 48.9 years in women with AWS and 58.1 years in women without AWS.They suggested that this difference was related to the BMI of these women,given than BMI increases with age.Another survey of 97 postoperative patients with breast cancer found that the average age of onset of AWS was 50 years,compared with an average age of 57 years of no onset of AWS.[4]

    Ethnic background

    African Americans are more likely to develop AWS[21]and axillary lymph node metastasis post-breast cancer surgery compared to Caucasians.[1,8]

    Systemic diseases

    Figueira et al.[17]recently reported that lymphadenectomy as well as hypertension were associated with an increased risk,while diabetes was associated with a decreased risk of cord development.The significance of hypertension and diabetes mellitus as risk factors for cord development in AWS should be evaluated in future studies.

    Surgical injury

    Injury to the intercostal nerve of the affected limb is associated with the occurrence of AWS.The average risk of AWS is 3.19 times higher after injury to an intercostal nerve than that after lymph node biopsy.[1]

    Pathology and pathophysiology

    When Moskovitz et al.[11]first identified AWS,they described fibrin blocks found in superficial veins and lymphatic vessels in the cord-like nodules and an association between these nodules and congestion and a hypercoagulable state in the superficial veins and lymphatic vessels.They suggested that the nodules are derived from lymphatic vessels and superficial veins.Wei et al.[2]used ultrasound to observe the cord-like nodules and found abundant blood flow signals and echoes of the same intensity in the blood vessels around the normal tissues.They proposed that the nodular structures were derived from blood vessels.Given their similar clinical manifestations,Moskovitz et al.[11]and Wei et al.[2]classified AWS as a type of Mondor's disease.Also known as spontaneous thoracic and abdominal thrombophlebitis,Mondor's disease is a type of a superficial venous thrombophlebitis that occurs in different parts of the body and is often characterized by sudden pain and cord-like swelling.[22]

    In recent years,histopathological and immunohistochemical staining,and ultrasound and nuclear magnetic resonance (NMR) imaging have been used to study AWS.The hypothesis of lymphatic origin of the nodules has gradually become accepted by increasing number of scholars.[3,23]Reedijk et al.[24]reported a case involving a female patient with amyotrophic lateral sclerosis (ALS)resulting from ALND.A biopsy showed fibroblasts surrounding lymphatic hyperplasia but no hemosiderin deposition (cases involving past bleeding or hemolytic diseases often show the deposition of hemosiderin in affected tissue).Rashtak et al.[3]reported a case of AWSbanded nodules after histopathological examination of sputum that involved nodular fibroblasts wound tightly around lymphatic vessels.Using immunohistochemical staining,they found a specific marker of lymphatic endothelial cells,D2-40,a specific antibody against O-chain glycoprotein with a relative molecular weight of 40,000,which reacts with lymphatic endothelial cells.This observation supports the hypothesis that the nodules of AWS originate from lymphatic vessels.

    Koehler et al.[23]used 18 Hz ultrasound to detect the nodular structure of AWS and did not find a specific structure associated with veins or fascia; however,they found a fibrin-rich protein bound to other interstitial structures in the abnormal tubular space.This finding contradicts the hypothesis that the cord-like nodules originate from the venous duct.Leduc et al.[25]used 17 Hz ultrasonography and 1.5 T Magnetic Resonance Imaging(MRI) to examine the nodules in 15 patients with AWS,which was diagnosed on the basis of the anatomy of the AWS cord-like nodules.Their findings were consistent with those for the axillary and upper limb lymphatic vessels,and MRI.The MRI images of the cord-like structure were similar to those of lymphatic vessels,and they concluded that the nodules originated from the lymphatics.

    AWS is considered to be a risk factor for lymphedema because of the similar pathophysiology of the two conditions.[26-27]Wariss et al.[26]conducted a prospective study on the relationship between AWS and lymphedema in 964 breast cancer patients followed-up for 10 years.The incidence rates were similar for AWS (35.9%) and lymphedema (31.4%),and they concluded that AWS was not a risk factor for lymphedema.

    DIAGNOSIS

    AWS is a complication that rarely attracts the attention of clinicians post axillary surgery.[11,13]Currently,physical examination is the gold standard for AWS diagnosis.[1]When a patient develops a cord-like nodule originating from the axilla postoperatively,some cord-like structures can also be observed in contact with the ipsilateral chest wall,underarm,arm,or elbow fossa or even the abdominal wall.[2]Plaques similar to the shape of a violin string and cord-like nodules can also spread to the back and the back of the hand.These cord-like nodules are associated with limb pain,limited abduction,and numbness and pain in the affected limb.The symptoms form the basis of the diagnosis of AWS.[3,6-8,11,16,18,25]AWS should be differentiated from acute lymphangitis,lymphadenitis,linear scleroderma,eosinophilic fascia(Schulman's syndrome),and thrombophlebitis.

    Leduc et al.[28]measured the length of nodules in 15 patients with AWS post-breast cancer surgery.The average length of the affected limb was 70.1 cm,and the average length of the nodules was 31.2 cm,or 44.5% of the length of the affected limb.Koehler et al.[15]selected 17 patients with AWS who were diagnosed with AWS within 12 weeks of surgery.The affected limbs of AWS patients were observed using 18 Hz ultrasound and were compared with the healthy limbs.The subcutaneous thickness,subcutaneous reflex,tissue structures,and echo intensity did not differ significantly between the limbs,which indicated that it might be difficult to diagnose AWS using ultrasound.

    Wei et al.[2]described a patient with breast cancer treated with secondary surgery who exhibited an axillary nodule 20 days after the first operation and on day 3 after the second operation.Extension of the affected limb was significantly limited from 150° to 90° and was accompanied by severe pain,and this patient's visual analog scale score for pain was 7 out of 10.Bergmann et al.[1]studied 193 patients with breast cancer after 45 days of follow-up and found that 5.4% of patients reported pain and 11.4% of patients exhibited limited upper limb movement.

    Nevola Teixeira et al.[8]developed an AWS screening questionnaire in conjunction with nurses,orthopedic surgeons,breast oncology surgeons,statisticians,and psychotherapists.The responses of 108 breast cancer patients,compared with the physical examination results,revealed a diagnostic sensitivity of 94% for this questionnaire for AWS.They also developed a preliminary diagnostic test for AWS.Patients with a total score≥3 points were suspected of having AWS.Using the scores of the screening questionnaire,two falsenegative patients were identified and their treatment was guided accordingly.However,Nevola Teixeira et al.[8]believed that the gold standard for AWS diagnosis is physical examination.The screening questionnaire can be used as a simple self-screening tool for a preliminary diagnosis.It also allows patients to better understand the symptoms of AWS,thereby increasing their awareness of AWS and possibly reducing the time between the onset of symptoms and treatment.

    TREATMENT

    AWS is a self-limiting disease.Moskovitz et al.[11]first described the condition and reported that AWS spontaneously healed in about 8 weeks in 42 of 44 patients and within 3 months in the other two patients.Some researchers later reported that the AWS nodules subside within 3 months.[11,13,29-31]However,in 10 of the 17 AWS patients studied by Koehler et al.[15],the symptoms persisted for more than 12 weeks.Torres Lacomba et al.[7]also found that two of 56 AWS patients still had symptoms after 3 months and the recovery rate was 96.4% instead of 100%.

    Springer et al.[31]performed preoperative limb assessment of 200 patients with breast cancer including related surgical risks,postoperative complications,and postoperative exercise guidance.They instructed the patients to exercise to improve flexibility,strength,and abduction in the affected limb.The patients' limbs were evaluated at 1,3,6,and 12 months postoperatively.Most patients recovered completely after 3 months,and all patients regained shoulder function akin to that in the preoperative state 12 months postoperatively.

    Symptoms of AWS,such as abnormalities in the affected limb,pain,and limb movement limitation,especially in breast cancer patients postoperatively,can easily cause anxiety.[25]AWS can also become a chronic disease,involving limited limb activity and pain,especially in the direction of abduction,[31]long-term muscle atrophy,[32]inflammation around the shoulder joint,and myofascial syndrome.[10]These long-term effects can reduce the quality of life and may become disabling.[8]To ensure that patients with diseases,such as breast cancer,return to normal health as soon as possible (both physically and mentally),it is important to increase their awareness about AWS.[5]Certain clinical interventions are necessary for such diseases,and clinicians and patients should be informed of the risk of upper extremity nodules postaxillary surgery,pain in the limbs,limited mobility,and interventions and treatments.[33]In addition to raising the awareness,clinical interventions included conservative treatment,such as physical therapy,medication,manual drainage,instrument-assisted soft tissue mobilization(IASTM),thoracic manipulation and stretching,manual axial distraction,percutaneous needle cord disruption with fat grafting and Xiaflex injection,and surgical treatment.

    Physical therapy

    Physical therapy includes hyperthermia,exercise,and strength training.[16,29]Tilley et al.[34]reported a case involving a 37-year-old breast cancer patient with AWS symptoms,such as limited abduction and the presence of nodules 2 weeks postoperatively.They recommended that the patient apply a heat pad daily to the axilla and inside of the arm,and to perform limb exercise,such as slow flexion of the arm and moderate abduction.The patient's symptoms improved considerably at week 7.

    A recently published study by Koehler et al.suggested that the treatment of AWS include manual therapy,exercise,education,and other rehabilitation modalities; however,they did not enlist surgery as a treatment modality.[35]A systemic review done by Yeung et al.[6]suggested that AWS frequency was reported in up to 85.4% of patients.Biopsies identified venous and lymphatic etiopathology,while five studies suggested lymphatic involvement.Twenty-one studies reported AWS occurrence within eight weeks postoperatively,but late occurrence of later than 3 months is possible.Pain was commonly reported along with shoulder abduction being more restricted than flexion.AWS symptoms usually resolve within 3 months but may persist.The risk factors might include extensiveness of surgery,younger age,lower body mass index,ethnicity,and healing complications.Low-quality studies suggested that conservative approaches,including analgesics,non-steroidal anti-inflammatory drugs,and/or physiotherapy may be safe and effective for early symptom reduction.

    Physical therapy is recommended as a safe and effective primary treatment for AWS.[6,14,35-44]Physical therapy treatment consists of an initial process of patient education,supervised and at-home exercises,and tissue “manipulations”,including a variety of adjunctive rehabilitation interventions,to improve range of motion and decrease pain.In addition,it also includes therapist-performed,in-clinic manual therapy,including myofascial release,soft tissue mobilization,and cord manipulation and stretching while the arm is abducted.[35]Other physical therapy techniques that have a positive effect on the outcome of AWS include compression bandaging,manual lymphatic drainage,scar release manipulation,massage of adhesion,joint mobilization,stretching and strengthening exercises,and at-home program.[35]Some patients are also afraid that the symptoms might be a sign of cancer recurrence;however,previous studies have reported no association between postoperative AWS and cancer recurrence.[27,45]Patient education and physical therapy treatment for AWS might help to reduce overall levels of patient anxiety.da Luz et al.[46]conducted a literature review to verify the physiotherapy treatment available for AWS after surgery for breast cancer in the context of evidence-based practice.From the 262 studies found,four articles that used physiotherapy treatment were selected.The physiotherapy treatment was based on lymphatic drainage,tissue mobilization,and stretching and strengthening.The four selected articles had the same outcome:improvement in arm pain and shoulder function and/or dissipation of the axillary cord.They concluded that studies that involved an interventional approach were rare and more randomized controlled trials are necessary to support the rehabilitation resources for AWS.

    Drug therapy

    Treatment for AWS includes analgesics,nonsteroidal anti-inflammatory drugs (NSAIDs),and proangiogenic drugs.[6]NSAIDs are mainly used for pain relief.Leidenius et al.[14]and Moskovitz et al.[11]reported that NSAIDs have no significant effect on AWS.Steegers et al.[19]studied postoperative chronic pain in 317 patients with breast cancer,with an average follow-up of 23 months.The overall chronic pain rate was 32% (103/317),and the pain occurred mainly in the chest wall,upper limbs,and back of the affected side.Persistent chronic pain in the ipsilateral limb was reported in 23% of patients who had not received ALND and 51% of patients who had received ALND.

    The presence of symptoms greatly affects the quality of life,and some patients rely on NSAIDs to relieve pain symptoms.Wei et al.[2]reported AWS treatment in a patient postoperatively.The patient presented with severe pain after abduction of the limb past 90°,and axillary nodules were visible to the naked eye.The patient was prescribed oral Aescuven Forte tablets (200 mg,one tablet twice a day) along with limb abduction exercise and massage of the axillary nodules for at least 30 minutes twice a day.The pain subsided after 1 week of treatment and abduction recovered to 150°.After 2 weeks of treatment,the pain disappeared,abduction was 170°,and nodules were significantly reduced.

    Discomfort early in the postoperative period increases the patient's psychological burden.Therefore,limb pain caused by AWS can affect the quality of life and limit the abduction range of motion of the affected limb.Therefore,appropriate use of analgesics to achieve psychological and/or symptomatic relief is helpful.In addition,some scholars believe that taking analgesics before performing limb exercise will reduce pain during the rehabilitation process.Schuitevoerder et al.[16]suggested that patients performed physical exercise while taking analgesics.They found that all patients recovered completely within a few weeks by taking only NSAIDs and performing simple limb exercises.

    In a controlled trial by Lauridsen et al.[47],139 eligible patients were randomized into two groups.Group A started exercise (stretching and flexibility exercises,strength training,and massage) 6 weeks postoperatively,and group B started same exercise 26 weeks postoperatively.Subjective and objective assessments were made postoperatively on the same day (phase 0),and then,7 weeks (phase 1),13-15 weeks (phase 2),25-27 weeks (phase 3),and 55-56 weeks (phase 4)postoperatively.The condition of the shoulder joint did not differ between the two groups after phases 0 and 1.By contrast,the shoulder joint in the affected limb was markedly better after phases 2 and 3 in Group A than in Group B.However,after phase 4,when Group B had begun exercises,the difference between the two groups was significantly smaller compared with the difference between the two groups after phases 2 and 3.These findings suggested that starting exercise as soon as possible postoperatively can reduce pain during the recovery process.

    Testa et al.[5]conducted a randomized controlled trial of 70 patients with breast cancer treated from 2001 to 2011 and evaluated the effectiveness of early physical therapy postoperatively.One week postoperatively,the patients started strength and posture training.The patient's movement of the affected limb (range of flexion,abduction,and elevation) were recorded,and pain was assessed according to a visual analog scale.Thirty-five patients in the control group did not participate in this early exercise training.The quality of life was compared between the treatment and control groups pre-and postoperatively.They reported that early postoperative physical exercise was essential for early recovery of the affected arm function and quality of life in the patients.

    Manual drainage

    One of the treatment modalities for AWS includes manual drainage.[7,36]AWS is caused mainly by poor lymphatic drainage and accumulation of proteins and inhibitors (e.g.NO synthase inhibitors).Manual drainage could help resolve this issue.Cho et al.[36]applied lymphatic drainage to 41 patients with AWS initially by health professionals and from the second week onwards by trained family members,3 to 5 times a week for 4 weeks.This convenient and effective method significantly reduced the pain,increased the mobility and muscle strength,and reduced the risk of postoperative lymphedema in the affected limb.The authors also compared the effects of physical exercise alone with those of physical exercise combined with manual drainage.The benefit of combined therapy was greater than that of physical therapy alone.

    Instrument-assisted soft tissue mobilization (IASTM),thoracic manipulation,stretching

    Crane et al.[48]treated a 48-year-old female patient with a past medical history of bilateral breast cancer with a bilateral latissimus dorsi flap reconstruction.They concluded that the utilization of an impairment-based physical therapy approach to treat a patient with AWS and thoracic dysfunction yielded positive outcomes.Further research on the efficacy of IASTM and physical therapy for the management of AWS is warranted.

    Manual axial distraction

    AWS-related cording on the chest wall may be difficult to detect and differentiate from Mondor's disease.[49]When cords are located on the chest wall,some doctors appear to consider AWS and Mondor's disease.[50]Mondor's disease is a thrombosis of a superficial chest wall vein and an uncommon complication of breast and axillary surgery.Although self-limiting,the subcutaneous cords may be both painful and functionally limiting for the patient,so the non-invasive technique of manual axial distraction was tested by Salmon et al.[50]Thirty consecutive patients with axillary Mondor's disease postoperatively were treated solely with this technique over a 24-month period.Mean age was 45 years (range:32-72) with 27 patients having undergone formal axillary dissection and three sentinel node biopsies.25 patients (83.3%) were successfully treated with a single procedure,three (10%)with two,and two (6.7%) with three procedures.The authors present the initial results of the novel technique of manual axial distraction that has been found to be efficacious and without any adverse effect.It provides a rapid and definitive cure for postoperative Mondor's disease.[50]

    Percutaneous needle cord disruption with fat grafting and Xiaflex injection

    Piper et al.[51]tested two novel treatment methods:1)percutaneous needle cord disruption with fat grafting,and 2) Xiaflex injection to the cording.AWS remains an incompletely understood postoperative phenomenon,the patients who develop severe cording often do not respond to traditional therapy and may require more aggressive treatment.They identified two new treatment modalities that markedly improved arm and shoulder range of motion,overall daily functioning,and pain.Aesthetic outcomes also improved with the softening of the cords.[51]

    Surgical treatment

    Surgical treatment is used mainly to remove AWS fiber cords to improve the quality of life of patients with severe symptoms.Surgery increases the risk of increased edema in patients.Considering the long-term effects on quality of life,routine surgical treatment for AWS is not recommended.[34]A most recent published paper by Koehler et al.suggested that the treatment of AWS included manual therapy,exercise,education,and other rehabilitation modalities,but did not consist of surgical treatment.[35]Physical therapy is recommended as a safe and effective primary treatment for AWS.[6,14,-44]Aggressive manual techniques and surgical intervention of the cord might not be appropriate.[35]

    SUMMARY

    AWS is a self-limiting disease that often occurs within 5 to 12 weeks post-axillary surgery and could be delayed to 180 days.Typical symptoms are cord-like nodules with pain and limited limb movement.In addition to physical symptoms,the lack of awareness of AWS causes anxiety and fear among the patients,which seriously affects their quality of life.The clinicians need to know more about the pathogenesis,histopathology,and effective treatment of AWS.Risk factors may include extensiveness of surgery,younger age,hypertension,lower body mass index,ethnicity,and healing complications.Physical examination is the gold standard for AWS diagnosis.Treatment may include physical therapy,drug therapy,manual drainage,instrument-assisted soft tissue mobilization (IASTM),thoracic manipulation,and stretching,manual axial distraction,percutaneous needle cord disruption with fat grafting and Xiaflex injection,and surgical intervention.Routine surgical treatment for AWS may not be recommended.Further clinical research is needed to provide more comprehensive diagnosis and intervention for patients suffering from AWS.

    ACKNOWLEDGEMENTS

    We thank Dr.Xiao-Jun Wang,the Chief of Plastic and Reconstructive Surgery department,for her full support and guidance to make this project possible.

    FINANCIAL SUPPORT AND SPONSORSHIP

    This work was supported by a grant from the Education Reforming Program,Peking Union Medical College (No.2015zlgc0111).

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