Sentinel Lymph Node Biopsy Replacing Axillary Dissection Series Of Studies

PartⅠ.The Audit Phase Study of Sentinel Lymph Node Biopsy in Clinical Node Negative Breast CancerObjective To study the value of sentinel lymph node(SLN)in breast cancer and the significances of sentinel lymph node biopsy(SLNB)in clinical node negative breast cancer patients.Material and Methods Four hundred and forty nine patients,registered in the Breast Center of Shandong Cancer Hospital & Institute from September 1999,were treated with SLNB followed by ALND using blue dye(Patent blue V or Methylene blue dye) and/or ^99mTc.Results For the 449 cases in the audit phase,SLNs were successfully identified in 438 of 449(97.6%)patients.The accuracy rate of SLNB to predict axillary lymph node status was 91.1%,with 21.3%false negative rate.The success rate,accuracy rate and false negative rate by blue dye and combined method were 96.6%,89.1%, 27.4%,and 100%,96.1%,8.5%,respectively.Ninety-eight percent of the SLNs were located at LevelⅠ.No relationships were found between the success rate,accuracy rate and age,tumor size,quadrant within the breast,pathological type,and the type of blue dye(p＞0.05 for all).Methylene blue had the same success rate and accuracy rate as Patent blue V.The false negative rate of the combined group was significantly lower than that of the blue dye only group(p=0.003).With the increasing of the number of SLNs detected,the false negative rate dropped significantly(p=0.001). Conclusions①SLNB could accurately predict the axillary status in clinical node negative breast cancer patients.②Most of the SLNs were located at Level I.③No relationships were found between the success rate,accuracy rate and age,tumor size, quadrant within the breast,pothological type,and the type of blue dye.④The false negative rate of the combined group was significantly lower than that of the blue dye only group.With the increasing of the number of SLNs detected,the false negative rate dropped significantly.⑤Methylene blue had the same success rate and accuracy rate as Patent blue V.⑥The accuracy rate of our audit phase was high enough for SLNB instead of ALND phase in clinical node negative breast cancer. PartⅡ.China Multicenter Study of Sentinel Lymph Node Biopsy Substituting Axillary Lymph Node DissectionBackground China Multicenter Study of Sentinel Lymph Node Biopsy(SLNB) Substituting Axillary Lymph Node Dissection(ALND)in Breast Cancer was conducted from Jan.2002,with 2,020 SLNB patients recruitment this June.The primary objectives were 5ys DFS and complications between SLNB and ALND.The second objectives included 5ys OS,SLN intraoperative diagnosis,Micrometastasis detection and prognosis,and radiologic safety.Materials and Methods Combined methylene blue dye and 99mTc-sulfur colloid or 99mTc-IT-Rituximab were used as tracers for SLNB.Patients with negative SLN did not receive ALND.Results The median age was 46ys.The median number of SLN was 2.Tumor size was less than 5cm,with mean size as 1.9cm.With the increase of the size and advance of the histopathology of the primary tumor,the positive rates of the SLN increased significantly(p=0.000,both).The types of the surgical were as fellows: BCS+SNLB 51.4%,Mastectomy+SLNB 26.1%,BCS+ALND 8.9%,and Mastectomy +ALND 13.6%,respectively.Mainly due to the difference of primary tumor sizes,the rates of BCS,SLNB substituting ALND,and the positivity of SLN were different among different centers.With a median fellow-up of 42 months in one early center--Shandong Cancer Hospital,two cases of axillary relapse(0.82%)were found in 244 SLNB cases(p＞0.05),while the complications of SLNB were significantly lower than that of ALND(p＜0.001).Conclusions:①First in China to condact prospective,multicenter study for SLNB substituting ALND for clinically early stage breast cancer,with 1970 cases enrolled;②Combined methylene blue dye and 99mTc-sulfur colloid or 99mTc-IT-Rituximab were used as tracers for SLN,with the successful rate of 100%;③SLNB techniche could avoid ALND for SLN negative patients(77.8%of clinically axillary negative cases in our study);④SLN positive rates increased significantly with the increase of the primary tumor size,which indicated that patients with small tumor should be selected first for SLNB substituting ALND in fresh hands;⑤The SLN positive rate was 3.5%in DCIS,which indicated that SLNB should be performed in patients with DCIS if they would receive mastectomy or breast reconstruction;⑥With short-term fellowup of 42 months in one center,SLNB could replace ALND for SLN negative patients with low axillary recurrence;⑦SLNB could decrease postoperative complications significantly,and improve the qulity of life for breast cancer patients.PartⅢ.Research on the Radiologic Safety of Sentinel Lymph Node Biosy in Breast CancerAims To study the radiologic safety of the sentinel lymph node biopsy(SLNB)in breast cancer.Material and methods SLN was detected with the combination of methylthionium and ^99mTc-sulfur colloid.The thermoluminescent dosimeters(TLD)were used to detect radiation dose received by patients and medical stuff in 40 cases of breast conserving surgery/mastectomy+SLNB from Oct.2006 to Jul.2007.The TLDs were set at the skin near the breast injection site,thoracic gland,and cavitas pelvis gonad of patients,and dominant hand index finger,thoracic gland,cavitas pelvis gonad and ocular lens of medical stuff.Results The mean radiation dose received at the breast injection site (5.946±5.023mSv)was significantly higher than that at the thoracic gland and cavitas pelvis gonad of the patients(both p=0.000).The mean radiation dose received at the different parts of different medical stuff had no significances(all p＞0.05),and were far lower than the basic criterion of radiological health protection set by the Department of Health of China.According to this criterion,it would be safe for surgeons to perform 1000 SLNBs annually.Conclusion The SLNB in breast cancer was radiologicallly safe both for patients and medical stuff,and no radiologic protection was needed during operation,it was sate for surgeons to perform 1000 SLNBs annually.PartⅣ.The Role of Lymphoscintigraphy in Sentinel Lymph Node Biopsy in Breast Cancer PatientsBackground Although preoperative lymphoscintigraphy in sentinel lymph node biopsy(SLNB)for breast cancer patients is undergone commonly,its clinical significance remains controversial.Methods We retrospectively analyzed our database that contained 636 consecutive breast cancer patients who received preoperative lymphoscintigraphy before SLNB.Results Among them,sentinel lymph nodes(SLN)were well imaged by lymphoscintigraphy in 86.5%patients,and SLN were located extra-axilla in 5.3% patients.The visualization of SLN in lymphoscintigraphy was not associated with histopathologic type,location and stage of primary tumor,and time interval from injection of radiocolliod to surgery.However,the negative lymphoscintigraphy results were associated with excision biopsy before injection of radiocolliod and positive axillary node statues.SLN was successfully detected in 625(98.3%)enrolled patients. Failure of surgical identification of axillary SLN was associated with whether hot spot was imaged by lymphoscintigraphy.However,we identified axillary SLN in 90 (90.9%)out of 99 patients with negative axillary findings in lymphoscintigram.The false negative rate of SLNB in our study was 16.0%(15/94)among patients of training group,and there was no significant difference in the false negative rate between patients who had axillary hot spot in lymphoscintigram and those who had not(P=0.273).Conclusions Visualization of SLN in preoperative lymphoscintigraphy predicted the successful SLN identification.However,it was less informative for the location of SLN during operation.Considering the complexity,time consumes,and cost of preoperative lymphoscintigraphy,it should be undergone for investigation purpose only at present.PartⅤ.Intraoperative Diagnosis Study of Sentinel Lymph Node in Breast CancerObjective Accurate intraoperative diagnosis of sentinel Lymph node(SLN)in breast cancer.Material and Methods Touch imprint cytology(TIC),pathological diagnosis with frozen section and Enhanced Polymer One-Step Staining(EPOS) immunohistochemistry were used for the intraoprative diagnosis of SLNs.Results The diagnoses of intraoperative TIC of 311 SLNs from 132 patients were as fellows:sensitivity 67.3%,specificity 95.0%,false negative rate 32.7%,false positive rate 5.0%,and accuracy 84.1%,respectively.The intraoperative pathological diagnoses with frozen section of 1237 SLNs from 375 patients were as fellows: sensitivity 92.7%,specificity 100%,false negative rate 7.3%,false positive rate 0,and accuracy 97.6%,respectively.The intraoperative EPOS diagnoses of 461 SLN from 125 patients were as fellows:sensitivity 95.3%,specificity 100%,false negative rate 4.7%,false positive rate 0,and accuracy 98.4%,respectively.The combined diagnoses of intraoperative frozen section and EPOS were as fellows:sensitivity 97.7%,specificity 100%,false negative rate 2.3%,false positive rate 0,and accuracy 99.2%,respectively.The combined diagnoses of intraoperative frozen and TIC were as fellows:sensitivity 95.7%,specificity 100%,false negative rate 4.3%,false positive rate 0,and accuracy 98.5%,respectively.Conclusion The combined intraoprative diagnosis of SLNs with frozen section and EPOS immunohistochemistry or TIC had very high accuracy and very low false negative rate,and could fulfil the clinical demand. PartⅥ.The Study of Micrometastasis Detection in Sentinel Lymph Node of Breast CancerBackground Assessment of lymph node involvement has been recognized as an integral part of breast cancer management,the standard procedure for a long time being complete axillary dissection with lymphadenectomy.However,up to two thirds of patients with T1 and T2 disease have a negative axillary dissection specimen and about half of them experience morbidity related to lymphadenectomy,including lymphedema,limb paresthesia,or infection.During the last few years,the microscopic evaluation of the axillary sentinel lymph node(SLN)has been established as a new procedure that is highly predictive of final axillary status.The small though not irrelevant risk of a false-negative result is outweighed by the prognostic information to be gained as well as by the minimization of local complications.Although SLN evaluation has emerged as an alternative staging procedure in initial breast cancer assessment,the extent of the pathologic examination described in the literature differs considerably between studies.A number of methods have been used,ranging from a simple approach to a more detailed assessment of the SLN at multiple levels on fresh or fixed tissue,with the aid of complementary cytokeratin immunostaining(CKI)or sophisticated molecular techniques to improve staging. Under dispute is how many nodal sections are needed to ensure an optimal yield and whether the histologic evaluation should include a multilevel,"near total" lymph node examination.Recently,it has been noted that a minor but not negligible proportion of patients with micrometastases(MMs,measuring＜2.0 mm)and isolated tumor cells (ITCs,measuring＜0.2mm)have evidence of non-SLN metastases in subsequent axillary dissection specimens.This observation supports the contention that examining the SLN by means of a limited number of sections may result in an underestimation of the metastatic potential of breast carcinoma.At this institution,SLN biopsy has become the method of choice for axillary staging in initial breast cancer assessment.Considering the various methods of SLN examination and the lack of consensus on the number of sections that should be routinely obtained from the SLN,particularly to detect MMs foci,we have retrospectively reviewed our series of "negtive" SLN results.The likelihood of finding metastatic deposits was comparable if sections were carried out at 100-,200-, 300-,400-,500-μm,and 1mm intervals.We assessed the overall yield of positive SLN results at different levels of sectioning and the optimal number of sections required to detect macrometastases and micrometastases and ITCs.Objective To study the pathological detection methods of micrometastasis in SLN and their clinical significance by step sectioned(SS)and for each level both H-E stain examination and IHC detection were performed.Then different detection methods were analyzed.We will discuss whether it is necessary for SS to take the place of single sectioning and the degree of the interval between each level;whether combined with IHC is a better method than SS pathological detection;the criterion of pathological diagnosis in SLN.Material and Methods Ninty-eight continuous women with breast cancer were included.200 SLNs of them was identified negative by standard hematoxylin and eosin(H-E)stain examination carried on initial levels.All SLNs were SS at 100μm intervals and for each level both H-E stain examination and IHC detection with AE1/AE3 were performed.Then different detection methods were analyzed for the rate of detection and the likelihood of finding metastatic deposits was comparable if sections were carried out at 100-,200-,300-,400-,500μm,and 1mm intervals.We assessed the overall yield of positive SLN results at different levels of sectioning and the optimal number of sections required to detect metastastic foci and MMs and ITCs.Results1.In 98 SLN negative cases,18 and 25 cases were found of upstaging in node status using SS and combined with IHC,therefore the positive detecting rate was increased by 18.4%and 25.5%,respectively.2.9 cases were found upstaging in node status using SS combined with IHC methods,the positive detecting rate was increased by 9.2%,and up to 27.2%.SS combined with IHC add significant yield if compared to SS with H-E stain(p=0.004). 3.In all 2175 slides,abnormal were found in 79 slides(3.6%)by SS,48(2.2%) more slides were found by SS combined with IHC.Significcance could be drawn in finding abnormal slides between the two methods(p=0.00).4.Rate of detection of MMs in 100-,200-,300-,400-,500-μm,and 1mm intervals by SS with H-E stain was 18.3%,14.3%,13.3%,12.2%,12.2%,7.1% respectively;intervals between 100- and 200-μm,300-μm did not add significant yield(p＞0.05).Conclusion1.SS H-E could significantly increase rate of SLN metastasis detection compared to the routine H-E pathological examination carried on initial levels.2.SS H-E combined with IHC could further significantly improve the detection of SLN MMs compared to SS H-E alone.3.300-μm might be the optimal interval for SS.