High-resolution MR lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer: preliminary results

Background  

The purpose of this study was to examine the utility of high-resolution magnetic resonance (MR) lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer.     

Sentinel lymph node biopsy in patients with breast cancer using superparamagnetic iron oxide and a magnetometer

Background

Some hospitals lack facilities for radioisotopes in sentinel node biopsy. A novel method is used with a superparamagnetic tracer and a magnetometer instead of a radioisotope.

Methods

Thirty patients were included in the study after obtaining IRB approval. Superparamagnetic iron oxide and patent blue dye were injected in the subareolar breast tissue. Following a few minutes of massage to promote migration of the iron tracer and blue dye throughout the lymphatic vessels, the axillary lymph nodes were detected transdermally using a handheld magnetometer and followed by standard axillary dissection in all patients.

Results

Of 30 patients evaluated, sentinel lymph nodes were identified in 90% (27/30) using both blue dye and magnetic tracer. Sentinel lymph nodes were identified using the magnetic method in 23/30 (77%) and blue dye in 24/30 (80%). There was one false-negative sentinel node, resulting in an overall sensitivity of 6/7 (86%).

Conclusions

This is the first study to use a magnetic tracer to identify sentinel lymph nodes in patients with breast cancer. This new technique may alter the role of radioisotopes with further refinement and experience.     

Tagging sentinel lymph nodes: a study of 100 patients with breast cancer

The aim of this study was to evaluate in breast cancer patients the feasibility of sentinel lymph node (SLN) identification and the sensitivity of this technique to detect node metastases. Between January and July 1997, SLNs were tracked with Evans Blue dye in 100 patients with breast cancer who then underwent complete level I/II axillary lymph node dissection (ALND). All SLNs were examined by haematoxylin–phloxin–saffron (HPS) staining and immunohistochemistry (IHC) of multiple sections. The findings for the SLNs were compared with results on ANLD. Axillary SLNs were identified in 83 patients (detection rate=83%; 95% confidence interval (CI) 74–90%). Axillary SLNs were detected in 58/83 cases (70%) at level I only, and in 69/83 (83%) at levels including level I. Histologically positive axillary SLNs were found in 45% (37/83) of patients, including 2 patients with malignancy (micrometastases) detected by IHC only. The sensitivity of axillary SLN to detect axillary lymph nodes metastases was 37/39=95% (95% CI 83–99%). SLNs of the internal mammary chain (IMC) were dissected for 33 tumours of the median or inner quadrants and detected in 26/33=79% of cases (95% CI 61–91%). In our experience, the overall sensitivity of SLN identification as a predictor of node (axillary or IMC) metastases was 41/43=95% (95% CI 84–99%), confirming the usefulness of the procedure.     

A randomized study comparing different doses of superparamagnetic iron oxide tracer for sentinel lymph node biopsy in breast cancer: The SUNRISE study

IntroductionThe non-radioactive method that uses the magnetic tracer (SPIO/Sienna) has shown to be a feasible technique for the SLN detection in breast cancer patients. The aim of this study is to assess the efficacy of different doses of a new magnetic tracer Sienna XP (Magtrace) compared to Tc-99 m and to evaluate its non-inferiority.MethodsPatients diagnosed with early-stage breast cancer cT1-3 N0, from October 2016 to August 2018 were eligible and consecutively randomized to three different doses of new SPIO used: group 1 (1 mL), group 2 (1.5 mL) and group 3 (2 mL).ResultsA total of 135 patients were included in the study, 45 in each group. Detection of SLNs with the three doses of Sienna XP (1 mL, 1.5 mL and 2 mL) showed non-inferior rates compared to the conventional technique with radiotracer (p = 0.654). Concordance by patients with SLN positive was 100% for all groups.83 (70.3%) patients reported skin staining at one month postoperatively, significantly lower in group 1 (p = 0.042). At 6 months follow up, group 1 remains with significantly lower skin discoloration (p = 0,01). In multivariate analysis, dose of 2 mL showed statistically significant for the skin staining. The majority of patients (70%) felt that skin discoloration does not represent a problem.ConclusionThe use of the Sienna XP magnetic tracer at 1 mL is not inferior to higher doses of magnetic tracer neither is inferior to radiotracer. 1 mL of magnetic tracer resulted in significantly less skin discoloration compared to higher doses.     

Extra-axillary sentinel lymph nodes in breast cancer

Background  Extra-axillary locations are known sites of lymph node metastases in patients with carcinoma of the breast. Methods  A technique utilizing a gamma probe was used to identify hot spots representing sentinel nodes residing in either axillary or extra-axillary locations in 680 patients with operable, clinically node-negative breast cancer. All identified sentinel nodes were excised. Results  Results showed that extra-axillary hot spots were found in 6.5% of patients. This rate increased to 14.8% if patients were injected with 8.0 ml unfiltered Technetium-99m-Sulfur colloid. Extra-axillary metastatic disease was identified in 6.8% of patients with extra-axillary hot spots. In patients with extra-axillary drainage, pathologically-positive nodes were exclusive to extra-axillary sites (ie, no axillary metastases) in 4.5% of cases. Factors found to increase the likelihood of identifying extra-axillary hot spots included; an increased volume of injection, medial or central tumor locations and T3 primary tumors. Conclusion  Gamma probe-guided techniques can identify extra-axillary sentinel nodes, which are at risk for harboring metastatic disease. Removal of these nodes can be done with little morbidity and may improve staging in the individual patient.     

乳腺癌前哨淋巴结淋巴细胞亚群的初步研究

目的　研究乳腺癌发生转移和未发生转移时前哨淋巴结 (sentinellymphnode,SLN)的免疫功能。方法　采用流式细胞技术 ,检测乳腺癌患者SLN中免疫细胞CD3 T、CD4 T、CD8 T、CD16 NK和CD19 B的改变 ,并与非SLN的检测结果进行比较。结果　肿瘤未发生转移时 ,SLN的CD3 T、CD4 T、CD8 T、CD16 NK、CD19 B数量与非SLN差异无显著性。当肿瘤发生转移时 ,SLN的CD4 T、CD8 T发生显著性改变 ,由正常的以CD4 T(6 9.0 7± 5 .0 2 )细胞为主 ,转变为以CD8 T细胞 (6 6 .15±5 .97)为主 ;而CD3 T、CD16 NK、CD19 B与肿瘤未发生转移的SLN相比 ,差异无显著性。结论　SLN免疫细胞数量与非SLN相比 ,差异无显著性。但肿瘤细胞转移后 ,改变了淋巴结的微环境 ,使淋巴结内CD4 T、CD8 T免疫细胞比例发生改变。     

Magnetic detection of sentinel nodes in oral squamous cell carcinoma by means of superparamagnetic iron oxide contrast

The aim was to evaluate sentinel node detection capacity by means of a magnetic probe in 11 patients with oral squamous cell carcinoma at stages T1-T2 received submucosal injections of a superparamagnetic iron oxide contrast agent (SPIO). A magnetic probe was used for sentinel node biopsy. The use of SPIO and magnetic probes in the early stages of oral cancer may offer an alternative to conventional radioisotope techniques and/or elective neck dissection.     

Predictors of positive axillary lymph nodes in breast cancer patients with metastatic sentinel lymph node

INTRODUCTION: Breast cancer with metastatic sentinel lymph nodes (SLN) may have clinico-pathologic factors associated with the presence of positive non-sentinel axillary nodes (NSLN). The aim of the present study was to determine factors that predict involvement of NSLN in breast cancer patients with positive SLN. MATERIAL AND METHODS: A prospective database search identified 80 patients who underwent SLN biopsy for invasive breast cancer between January 1999 and August 2002. Clinico-pathologic data was analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: A total of 23 patients had positive SLN and underwent conventional axillary lymph node dissection. Statistical analysis revealed that lympho-vascular invasion (p~0.00000), SLN metastasis >2 mm (p=0.002), and the presence of extra-nodal involvement (p=0.002), were positive predictors of the metastatic involvement of NSLN. CONCLUSIONS: The likelihood of positive NSLN correlates with pathologic parameters such as the presence of lympho-vascular invasion, size of the SLN metastasis, and extra-nodal involvement. These data may be helpful with the regard to the decision to undertake axillary dissection in breast cancer patients with metastatic sentinel lymph nodes.     

The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment

The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium‐sulphur colloid (^99mTc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag^®, which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non‐inferiority of SentiMag^® vs. ^99mTc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between ^99mTc and SentiMag^® was 97.9%. The DR per patient was 99.0% for ^99mTc and 97.9% for SentiMag^®. SentiMag^® appears to be non‐inferior to the radiotracer and safe. While ^99mTc remains the standard, SentiMag^® DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+^® allows effective treatment of breast cancer patients.     

MR间质淋巴造影在VX2兔乳腺癌内乳前哨淋巴结显像中的初步研究

背景与目的：内乳淋巴结(internal mammary lymph node,IMLN)对乳腺癌远处转移及远期复发的预测价值与腋窝淋巴结的价值相当。IMLN在改良根治术下不能被清除,目前临床上只能对内乳区可能存在转移的患者盲目追加放疗;如何选取适合IMLN活检或切除手术的乳腺癌患者,则是目前临床急需解决的问题。该研究初步探讨MR间质淋巴造影(MR lymphography,MR-LG)检查在显示VX2兔乳腺癌内乳前哨淋巴结(sentinel lymph node,SLN)的可行性。方法：选取纯种雌性新西兰大白兔55只建立VX2兔乳腺癌动物模型,并行MR-LG检查。图像传至ISP(Philips Intellispace Portal)工作站进行后处理,自注射部位至内乳或腋窝方向的引流淋巴管上最先显像的1个或数个淋巴结定义为SLN,记录SLN及引流淋巴管显示情况,并与前哨淋巴结活检(sentinel lymph node biopsy,SLNB)结果对照。结果：55只实验兔建模成功率为98.2%(54/55),最终51只荷瘤兔成功入组。在MR-LG图像上,对比剂注射后5 min扫描较注射后即刻扫描可显示更多的内乳区淋巴管(36 vs 25),且同时显示腋窝SLN及引流淋巴管效果进一步提高(45 vs 37),两者差异均有统计学意义(P=0.021和P=0.040)。在内乳区MR-LG图像上,显像SLN长径为(2.64±0.59)mm,短径为(2.24±0.54)mm,引流淋巴管直径平均值为2.18 mm;肿瘤大小及腋淋巴结数目对内乳淋巴管的显示差异均有统计学意义(P=0.032和P=0.040)。11只荷瘤兔内乳区SLNB共检出内乳区SLN 15枚,位于第2~3肋间者6枚,1~2肋间者5枚,3~4肋间者2枚,而位于第10肋间和剑突旁者各1枚;对照MR-LG,共9只荷瘤兔共显示11枚内乳区SLN,其中7只(77.8%,7/9)与SLNB显示结果一致;SLNB检出的SLN长短径均大于MR-LG图像上显示的SLN,差异均有统计学意义(P<0.05)。结论：MR-LG可显像VX2兔乳腺癌内乳区SLN,但显像率的提高有待进一步研究。     

乳腺癌前哨淋巴结规范化处理

前哨淋巴结活检术（sentinel lymph node biopsy, SLNB）标志着乳腺癌淋巴结手术进入微创时代,循证医学I类证据支持SLNB是临床腋窝淋巴结阴性早期乳腺癌患者安全、有效的腋窝诊断技术,前哨淋巴结阴性及低肿瘤负荷患者行SLNB替代腋窝淋巴结清扫术后,腋窝淋巴结复发风险和并发症极低。作为乳腺癌区域淋巴结微创诊断技术,SLNB安全有效替代腋窝淋巴结清扫术应建立在规范化操作前提下。目前SLNB在我国早期乳腺癌患者中逐渐趋于规范化和普及化,本文将对临床实践中SLNB的适应证、示踪剂应用、学习曲线掌握、手术规范操作和组织标本处理等问题进行综述。      

Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients

BACKGROUND:

Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN‐positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery.

METHODS:

The authors retrospectively reviewed the records of 326 patients with breast cancer who underwent IF analysis of SLNs at a single institution. Then, they conducted a meta‐analysis that included 47 published studies of IFS of SLNs in patients with breast cancer.

RESULTS:

Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group) and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6% (60 of 99 patients), and overall specificity was 100% (227 of 227 true negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group (28.9%) than in the MAM group (80.3%; P < .0001). According to the meta‐analysis of published studies and data from the author's institution (47 studies, for a total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was 94% for the MAM group and 40% for the Mi/ITC group.

CONCLUSIONS:

IFS of SLNs was more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked sufficient accuracy to rule out Mi/ITC deposits. Cancer 2011. © 2010 American Cancer Society.     

Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study

Background: The prognostic meaning and thus indication for adjuvanttherapy of lymphogenic micrometastases in breast cancer patientsis still under debate. Patients and methods: From 1999 to 2007, 703 patients with _cT_1–2N₀breast cancer underwent surgery including sentinel lymph nodebiopsy. Examination of sentinel lymph nodes consisted of hematoxylinand eosin and immunohistochemistry staining following serialsectioning of the sentinel node. Patients were divided intofour groups: _pN₀ (n = 423), _pN_1micro (n = 81), _pN_1a (n = 130)and _pN_1b (n = 69). Median follow-up was 40 months. Results: At the end of follow-up, 53 patients had died and 64had recurrent disease. Compared with _pN₀ and following adjustmentfor possible confounders, including adjuvant systemic treatment,overall survival was not significantly different for _pN_1microwhile significantly worse for _pN_1a and _pN_1b {hazard ratio (HR)[95% confidence interval (CI)]: 0.59 [0.14–2.58], 4.31[1.85–10.01], 10.66 [4.04–28.14], respectively}.Likewise, disease-free survival was not significantly differentfor _pN_1micro and worse for _pN_1a and _pN_1b (HR [95% CI]: 1.43[0.67–3.02], 2.79 [1.37–5.66], 7.13 [3.27–15.54],respectively). Distant metastases were more commonly observedin the _pN_1micro than in the _pN₀ group, but still not as commonas in the _pN_1a or _pN_1b group (HR [95% CI]: 4.85 [1.79–13.18],10.34 [3.82–28.00], 23.25 [7.88–68.56], respectively). Conclusion: Although the risk of distant metastases was higherin patients in the _pN_1micro than in the _pN₀ group, no statisticallysignificant differences were observed in overall or disease-freesurvival between _pN₀ and _pN_1micro. Micrometastatic lymph nodeinvolvement in itself should not be an indication for adjuvantchemotherapy in breast cancer patients. Key words: breast cancer, micrometastases, prognosis, sentinel lymph node Received for publication March 11, 2008. Revision received June 25, 2008. Accepted for publication July 1, 2008.     

临床腋窝淋巴结阳性乳腺癌患者内乳区前哨淋巴结活检术研究*

目的：评估临床腋窝淋巴结阳性乳腺癌患者行内乳区前哨淋巴结活检术（IM-SLNB）的临床意义。方法：2013年6 月至2014年10月对山东省肿瘤医院乳腺病中心就诊的64例临床腋窝淋巴结阳性的原发性乳腺癌患者行前瞻性单臂入组研究,采取腋窝淋巴结清扫术,同时均应用新的核素注射技术进行IM-SLNB。结果：64例患者中内乳区前哨淋巴结（IM-SLN）显像为38例,显像率为59.4%（38/ 64）。 38例IM-SLN 显像患者中IM-SLNB 成功率为100%（38/ 38）,并发症发生率为7.9%（3/ 38）,IM-SLN 转移率为21.1%（8/ 38）。 肿瘤位于内上象限和腋窝淋巴结转移数目较多的患者,其IM-SLN 转移率较高（P < 0.001 和P = 0.017）。 患者临床获益率为59.4%（38/ 64）,其中12.5%（8/ 64）另接受了内乳区放疗、46.9%（30/ 64）避免了不必要的内乳区放疗。结论：临床腋窝淋巴结阳性的乳腺癌应进行IM-SLNB,尤其对于肿瘤位于内上象限及怀疑存在较多腋窝淋巴结转移数目的患者,以获得内乳区淋巴结的转移状态,指导乳腺癌患者内乳区放疗。     

Stereoscopic scintigraphic imaging of breast cancer sentinel lymph nodes

BACKGROUND: Lymphoscintigraphy is used preoperatively to identify sentinel lymph nodes (SLNs). Conventional planar scintigraphy cannot provide three-dimensional(3D) information for SLN biopsy. We applied stereoscopic imaging to preoperative lymphoscintigraphy to obtain 3D information and evaluated its usefulness. METHODS: Forty-four clinical stage I breast cancer patients (1 male, 43 females; age, 59.4+/-11.4 years) were enrolled in this study. Three hours after the injection of Tc-99m, 10 degrees of oblique images and routine anterior and lateral images were acquired. Anterior and lateral stereoscopic images were obtained in all studies, except for 2 patients; only lateral views were done for those. Two experienced radiologists enumerated the visualized hot nodes. RESULTS: Stereoscopic imaging delineated more hot axillary lymph nodes compared to routine planar imaging in 8 of 42 patients (19.0%) on anterior view, 5 of 44 patients (11.4%) on lateral view, and 11 of 44 patients (25.0%) on either the anterior or lateral view. Statistically significant differences were observed between stereoscopic and routine planar imaging method on the anterior (p=0.012) and the lateral views (p=0.043). The stereoscopic imaging provided 3D information and effectively separated closely located hot nodes that were viewed as one hot node on conventional planar images. Thirty-eight out of 42 cases (90%) with anterior stereoscopic images identified the same number or more axillary hot nodes compared with lateral stereoscopic images. CONCLUSION: The stereoscopic imaging method could improve the preoperative identification of SLNs. This method is technically simple, and could be a powerful diagnostic tool for SLN imaging breast cancer.     

乳腺癌前哨淋巴结微小转移的检测

目的探讨检测乳腺癌前哨淋巴结(SLN)微小转移的最佳方法,研究临床病理因素与微小转移的相关性。方法应用同位素法检测乳腺癌SLN;对常规病理检查阴性的SLN,以100μm为间隔,进行多层间隔连续切片,并做HE和免疫组化染色检测微小转移;取肿瘤标本进行连续切片,并行免疫组化染色。结果共检测59例患者的121枚SLN和44份肿瘤标本,有14例(23.7%)患者的17枚(14.O%)SLN有微小转移。用HE染色法,切片数量从1层增加到3层时,微小转移的检出例数分别为3、7和10例;在3个层面上行间隔连续切片,HE分别与AE1/3、CK19和muc1联合检测时,微小转移的检出例数分别为14、12和16例。增加切片数量或采用联合检测的方法,可以提高微小转移的检出数量,微小转移与原发肿瘤大小、c-erbB2、MMP-2和血管内皮生长因子(VEGF)的表达相关。结论检测SLN微小转移的最佳方法为间隔100μm、在2个层面上行间隔连续切片,同时进行HE和muc1染色,可以检出绝大多数的微小转移。