Clinical Study On The Rule Of Axillary Lymph Node Metastasis And Upper Extremity Lymphatic Drainage System In Patients With Breast Cancer

BACKGROUND:At present,breast cancer has beeome one of the main diseases threatening the health of women,and the incidence has been increasing year by year.Axillary lymph node metastasis is the most common form of metastasis in breast cancer patients.It is also one of the important causes of its poor prognosis.Axillary lymph node dissection became an important part of surgical treatment of breast cancer.On the one hand,axillary lymph node dissection can remove metastatic lymph nodes,reduce tumor burden and recurrence and metastasis rate.On the other hand,it can assess the status of the entire axillary lymph node,Provide a basis for pathological staging,and provide a basis for patients to develop a reasonable diagnosis and treatment plan after surgery.However,excessive dissection will inevitably result in corresponding complications such as lymphedema.pain,numbness and weakness of the affected upper limb,limited movement of the shoulder and so on,which can bring to the patients with physical and psychological double trauma.In recent years,with the continuous development of modem surgery,the surgical treatment of breast cancer has also changed.The treatment of axillary lymph nodes has evolved from single axillary lymph node dissection to sentinel lymph node biopsy(sentinel lymph node biopsy,SLNB)and axillary lymph node dissection.SLNB has become one of the standard clinical treatment in early invasive breast cancer patients with axillary lymph node-negative,which retained the axillary lymph node with normal function without metastasis in the affected side and reduced the occurrence of postoperative upper limb lymphedema.But there was still 2%-7%of patients with upper limb lymphedema after SLNB alone.Secondly,axillary reverse mapping(ARM)technology uses a tracer to show the lymph nodes and lymphatic vessels draining the upper extremities and preserving them,thus preventing postoperative upper extremity lymphedema.With the deepening of the research,SLNB and ARM technologies are challenged,such as low detection rate,high false negative rate,whether sentinel lymph node can predict the whole axillary lymph node status,skip metastasis,oncology safety of ARM procedure.Therefore,this study will analysis the clinical and pathological data of breast cancer patients,combined with ARM technology and the application of SLNB,to more comprehensively understand the rules of axillary lymph node and upper limb return lymphatic drainage in breast cancer patients,in order to guide the comprehensive treatment of breast cancer and provides a useful reference for prevention of upper limb lymphedema after SLNB.METHODS AND RESULTS:In the present study,we intended to study the metastasis pattern of axill ary nodes and upper limb reflux lymph nodes in breast cancer patients,then explore the relationship between them,including the following three aspects:Part Ⅰ Distribution and metastasis pattern of axillary lymph nodes in breast cancer patientsMETHODS:This study will retrospectively analyze the clinicopathological data of female breast cancer patients who received axillary lymph node dissection in Qilu Hospital of Shandong University between 2013 and 2016.The clinicopathologic factors such as age,ethnicity,menarche age,marital status,fertility status,BMI(Body Mass Index,BMI),axillary lymph node metastasis,pathological type of tumor,histological grade,side(left or right),the number of tumors,tumor size,invasion of skin,invasion of vascular status,expression of hormone receptors,expression of HER2,expression of Ki67 were analyzed,evaluate the distribution and metastasis pattern of axillary lymph nodes,and summarize the characteristics of axillary lymph node metastasis in different pathological types and molecular breast cancer patients.RESULTS:1.The axillary lymph nodes were mainly distributed in the lateral margin of the pectoral muscle(Level I),and the number of lymph nodes in levelⅠ group was significantly higher than that of the other regions,The metastatic rate of lymph nodes in latissimus dorsi muscle was high.2.The age of the patient,menarche age,BMI index,histological grade of the tumor,tumor size,vascular invasion,lymphatic invasion and the ki67 expression level were related to the axillary lymph node metastasis of the patients with breast cancer(p<0.05).Multivariate analysis showed that histological grade,tumor size,vascular invasion,lymphatic invasion and Ki67 expression were independent risk factors for axillary lymph node metastasis in breast cancer(P<0.05);3.Tumor size,skin invasion,vascular invasion,lymphatic invasion,metastasis of the lymph nodes in level Ⅰ and level Ⅱ groups,metastasis of the lymph nodes between the pectoral muscles and the number of lymph node metastases in level Ⅰ and level Ⅱ groups were related to the lymph node metastasis in level 3(p<0.05).Multivariate analysis showed that skin invasion,metastasis of the intermuscular lymph nodes,and lymph node metastasis in level Ⅰ and level Ⅱ were independent risk factors for lymph node metastasis in level 3(p<0.05);4.The most common way is to skip the level Ⅰ lymph nodes and have the level Ⅱ lymph node metastasis,and the HER2 expression status of the patients was related to the skip metastasis of the axillary lymph node(p<0.05).Part Ⅱ Distribution and metastasis pattern of upper limb reflux lymph nodes in breast cancer patientsMETHODS:In this study,axillary reverse mapping(ARM)was performed with indocyanine green tracer to observe the distribution and metastasis pattern of lymph nodes in the upper limbs of breast eancer patients and evaluate the feasibility of ARM technology and oncology safety.RESULTS:1.Indocyanine green has the characteristics of real-time development of lymph nodes and lymphatic vessels.The success rate of ARM lymph node tracing is 95.9%(47/49).A total of 182 ARM lymph nodes were detected,with an average of 3.9 per patient and a maximum of 12 ARM lymph nodes were detected,and at least 1 ARM lymph node was detected in a patient respectively.2.The distribution of ARM lymph nodes:111 lymph nodes(61%)were located between the superior and inferior margins of the axillary vein and the second intercostal brachial nerve.Between the thoracodorsal vascular bundle and the anterior latissimus dorsi;33 lymph nodes(18%)were located between the iliac vein and the second intercostal nerve,and the inner and outer margins are located between the anterior serratus and the thoracodorsal vascular bundle.The upper edge of the 24 lymph nodes(13%)was located below the second intercostal brachial nerve,the inner and outer margins were located betAveen the thoracodorsal nerve vascular bundle and the anterior serratus;the upper edge of the 3 lymph nodes(2%)were located below the second intercostal brachial nerve,the inner and outer margins are located between the thoracodorsal vascular bundle and the anterior latissimus dorsi;11 lymph nodes(6%)were located above the axillary vein.Most of the ARM lymph nodes were located between the iliac vein and the second intercostal brachial nerve(144/182,79%);3.The invasion of the ARM lymph nodes:the positive rate of the patients with positive ARM lymph node was 14.9%(7/47),a total of 17 ARM lymph nodes were positive(17/182,9.3%),and the positive rate of ARM lymph nodes was 25.9%(7/27)in patients with axillary lymph node-positive breast cancer,In patients with axillary node-negative breast cancer,ARM lymph nodes were negative(0/20).Part m Relationship between upper limb reflux lymph nodes and axillary sentinel lymph nodes in patients with breast cancerMETHODS:Axillary reverse mapping(ARM)was performed using indocryanine green(ICG)to find the upper extremity lymphatics.Sentinel lymph node biopsy(SLNB)was performed using methylene blue dye(MBD).We wanted to know if the lymphatic drainage of the upper extremity is completely independent of the breast,studying the clinical pathological relationship between them.RESULTS:1.Forty-nine patients were treated with methylene blue as a tracer for SLNB.The success rate of SLN tracer was 93.9%(46/49).A total of 80 blue-stained SLNs were found,with an average of 1.9 SLN per patient.A maximum of 4 SLNs were detected,and at least 1 SLN was detected in a patient respectively.78 SLNs located in the lateral margin of the middle part of the pectoralis major,along the surface of the lateral thoracic vein and the second intercostal arm(78/80,97.5%),2 SLNs located in the lateral margin of the axillary(2/80,2.5%).2.Of all the 44 patients who successfully underwent SLNB and ARM procedures,we found the convergence between the upper extremity and the breast through the same node in some patients.The SLN was the same as the ARM node in 5 patients(5/44,11.4%).The ARM node was the same as the node which lies in the next station of the SLN(designated posterior SLN)in 4 patients(4/44,9.1%).In the remaining 35 patients,the nearest distance(D,cm)between the SLN and ARM node was 0 in 3 patients(3/44,6.8%),0<D<1 in 7 patients(7/44,15.9%),1<D ≤2 in 10 patients(10/44,22.7%),2<D<3 in 7 patients(7/44,15.9%),3<D ≤4 in 3 patients(3/44,6.8%),4<D ≤5 in 3 patients(3/44,6.8%),and>5 in 2 patients(2/44,4.5%).CONCLUSIONS:1.The axillary lymph nodes of the breast cancer patients were mainly located in the lateral margin of the pectoral minor muscle.The common way of metastasis is from the low level to the high level,and the skip metastasis is also present.The metastasis of the level 3 lymph node group should be noted during the operation,and the metastasis of the axillary lymph nodes can be predicted by the clinical pathological characteristics;2.The ARM nodes are most located between the axillary vein and the second intercostobrachial nerve.ARM using indocryanine green has the characteristics of real-time development of lymph nodes and lymphatic vessels,the operation process is simple,and the detection rate of ARM lymph nodes is high.ARM is oncologically safe and the results are accurate and reliable;3.The anatomical location of the ARM lymph nodes is closely related to the SLN.Most of the ARM nodes are located in the SLNB area.There is a crossover between the ARM node and the SLN,which provides the anatomical support for upper limb lymphedema after SLNB.SIGNIFICANCE:On the one hand,this study analyzed the distribution characteristics of axillary lymph nodes and upper limb return lymph nodes in breast cancer patients.The fluorescence imaging method was used to trace ARM lymph nodes,blue dye method was used to trace SLN,and the anatomical localization relationship were analyzed between them;On the other hand,the clinicopathologic factors such as patient’s age,ethnicity,menarche age,marital status,fertility status,BMI index,histological grade of tumor,location of tumor,number of tumors,tumor size,skin invasion,vascular invasion,lymphatic invasion and Ki67 were analyzed.The above results reveal the distribution and metastasis of axillary lymph nodes and upper extremity lymph nodes in breast cancer patients.It is helpful to guide the surgical treatment of patients with breast cancer,and also provide anatomic basis for the prevention of upper limb lymphedema after SLNB surgery.