早期乳腺癌腋窝前哨淋巴结活检的研究现状

自从1894年Halsted创立了乳腺癌根治术以来,腋窝淋巴结清扫术(axillary lymph nodes dissection,ALND)一直是乳腺癌外科治疗的重要组成部分,对临床分期、判断预后、指导治疗以及防止局部复发具有非常重要的临床意义。近年来     

早期乳腺癌前哨淋巴结活检术的临床应用

目的探讨应用前哨淋巴结活检（SLNB）技术预测腋窝淋巴结状态的准确性。方法应用同位素示踪法联合亚甲蓝染料示踪法对68名临床腋窝阴性的早期乳腺癌患者行前哨淋巴结活检术,然后行腋窝淋巴结清扫术（ALND）。对照前哨淋巴结情况与腋窝淋巴结状态的关系,分析SLNB的临床意义。结果68例患者中检出前哨淋巴结（SLN）66例,检出率为97．06％,共检出SLN192枚,平均每例2．91枚。66例中,34例SLN阴性患者中,2例为假阴性,假阴性率为5．88％。当SLN阴性时,SLNB预测腋窝淋巴结状态的准确率为94．12％。SLNB检测腋窝淋巴结转移情况的灵敏度为94．12％,特异度为94．12％,SLNB与ALND结果的一致率为77．27％。结论联合应用染料示踪法和同位素示踪法行SLNB具有较高的检出率,SLNB能较准确的预测腋窝淋巴结的转移情况。     

早期乳腺癌前哨淋巴结活检替代腋窝淋巴结清扫的临床应用研究

目的 对前哨淋巴结活检(sentinel lymph node biopsy,SLNB)替代腋窝淋巴结清扫(axillary lymph node dis-section,ALND)在早期乳腺癌患者中的应用以及安全性研究及探讨.方法 回顾性分析行SLNB和ALND手术的503例早期乳腺癌病例,对患者住院时间、拔管时间及住院费用进行对比,以及对患者上肢并发症、腋窝局部复发及远处转移情况进行随访,随访至2016年06月,中位随访时间为32(6 ～52)个月.结果 在住院时间、拔管时间、住院费用以及上肢并发症方面,SLNB组明显优于ALND组,差异有统计学意义,而在腋窝局部复发及远处转移情况方面两组无统计学意义.结论 在SLN阴性早期乳腺癌中,SLNB与ALND可以取得相同的疗效,而且,SLNB与ALND相比,手术创伤小,麻木疼痛、肩关节活动受限等术后并发症明显减少,且可缩短患者住院时间,减轻患者的经济负担.     

乳腺癌前哨淋巴结活检研究进展

近年来,乳腺癌的发病率越来越高,乳腺癌治疗方式也在不断改进,但手术仍然是早期乳腺癌治疗的主要手段。对于早期乳腺癌,前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）是一种安全、精确的手术方式,已逐渐替代腋窝淋巴结清扫术（axillary lymph node dissection,ALND）成为早期乳腺癌治疗的标准术式。随着研究的深入,SLNB的应用范围更广,术后生活质量显著改善,但其操作尚需要进一步统一规范。在前哨淋巴结微转移、宏转移、前哨淋巴结活检阳性的老年患者以及新辅助化疗的前哨淋巴结活检等方面尚未达成共识,还需要更多大型多中心前瞻性的随机试验来进一步论证。     

乳腺癌前哨淋巴结活检的外科新观念

1历史回顾1894年美国医生Halsted在约翰·霍普金斯医院开创乳腺癌根治手术,即整块广泛切除患肿瘤组织包括全乳房、胸肌及区域淋巴结,使术后复发率由当时的58％－85％下降到6％,同时也使肿瘤器官的广泛切除加区域淋巴结清扫成为肿瘤外科治疗的原则,推动了近代肿瘤学的发展。50至70年代,Halsted手术受到了清扫范围扩大到胸骨旁、锁骨上或前上纵隔的扩大手术的冲击,但后者疗效并不比前者优越,加之术后形体不佳,手术并发症高,在历史的进程中被自然淘汰。70年代美国学者Fisher明确指出：乳腺癌是一种全身性疾病,癌细胞转移无固定模式…     

前哨淋巴结时代乳腺癌的精准区域处理：演进与展望

区域淋巴结状况是乳腺癌重要的预后指标之一,可以指导分期和辅助治疗策略的制定。近30年来乳腺癌前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）研究发展迅速,循证医学Ⅰ类证据支持其为临床腋窝淋巴结阴性早期乳腺癌患者安全、有效的腋窝分期技术,前哨淋巴结阴性及低肿瘤负荷患者SLNB替代腋窝淋巴结清扫术后腋窝复发风险和并发症极低。乳腺癌局部区域控制新理念——应该综合考虑远处转移风险、全身治疗效果与不良反应以及局部区域治疗（手术/放疗）效果与不良反应——推动了SLNB适应人群不断扩展,新辅助治疗与SLNB、内乳SLNB将进一步促进区域淋巴结处理降阶梯,豁免腋窝手术临床研究值得期待。SLNB标志着乳腺癌区域淋巴结迈入微创化精准诊疗时代。本文就前哨淋巴结时代乳腺癌的精准区域处理的演进过程和最新进展进行总结,以期为广大临床工作者提供参考。     

乳腺癌前哨淋巴结定位和活检

目的：难证乳腺癌前哨淋巴结定位和活检技术的可行性和前哨淋巴结的组织状况能否准确预告腋淋巴结的状况。方法：本研究使用专利蓝,对３３例乳腺癌患者进行了术中及术后前哨淋巴结定位和活检术。结果：３０例（９１％）找到前哨淋巴结,前哨淋巴结预告腋淋巴结的准确率为９６．７％,假阴性１例。结论：本研究结果证实,乳腺癌前哨淋巴结定位和活检技术是可行的,前哨淋巴结的组织学特征能够准确反映腑淋巴结的状况。我们相信在将来     

乳腺癌前哨淋巴结的临床研究进展

探讨乳腺癌前哨淋巴结活检技术的临床应用和进展。回顾国内外有关乳腺癌前哨淋巴结(SLNB)的相关文献报道,对乳腺癌前哨淋巴结的方法,评估,临床应用适应证,并发症进行分析。     

乳腺癌前哨淋巴结活检30例分析

目反同位素为示踪剂探测乳腺癌前哨淋巴结（ｓｅｎｔｉｎｅｌ ｌｙｍｐｈ ｎｏｄｅ,ＳＬＮ）,并根据前哨淋巴结活检和腋淋巴结清扫的病理结果,评价前哨淋巴结预测腋窝淋巴结转移的准确性。方法：研究对象为自２０００年５月份起我院乳腺科收治的３０例Ｔ１－２Ｎ０的乳腺癌患者,使用＾９９ｍＴｃ－硫胶体（＾９９ｍＴｃ－ｓｕｌｐｈｕｒ ｃｏｌｌｏｉｄ）为示踪剂,用Ｇａｍｍａ探测仪进行前哨淋巴结探测活检,之后行腋窝清扫。结果：２７例患者中成功地发现了ＳＬＮ,发现率为９０％（２７／３０）,前哨淋巴结的数量为１－３个,平均每例１．５个,非前哨淋巴结（ｎｏｎｓｅｎｔｉｎｅｌ ｎｏｄｅ）５－２０个,平均数１３．３个,２７例ＳＮＢ成功的患者中１４（５２％）例有腋窝淋巴结转移,前哨淋巴结未发现转移而非前哨淋巴结有转移的有２例,假阴性率７．４％（     

1个前哨淋巴结阳性乳腺癌患者的腋窝非前哨#br# 淋巴结转移情况及危险因素分析#br#

目的研究1个前哨淋巴结阳性的乳腺癌患者腋窝非前哨淋巴结（NSLN）转移情况及危险因素,为该类患者豁免腋窝淋巴结清扫（ALND）提供指导。方法选取2013年1月至2020年12月在哈尔滨医科大学附属肿瘤医院行前哨淋巴结活检（SLNB）证实仅有1个前哨淋巴结阳性且行ALND的乳腺癌患者465例,根据其腋窝NSLN转移情况,分为NSLN转移组104例,NSLN未转移组361例。比较两组的一般资料,采用二元Logistic回归分析腋窝NSLN转移的独立影响因素。结果465例仅1个前哨淋巴结转移的乳腺癌患者中,104例（224%）发生腋窝NSLN转移。其中,多个亚组患者的腋窝NSLN转移率<10%,如肿瘤T1a+b期的NSLN转移率仅91%、肿瘤T1期且前哨淋巴结数量＞5个的腋窝NSLN转移率仅70%等。单因素分析结果显示,NSLN转移组与NSLN未转移组前哨淋巴结数、肿瘤T分期差异有统计学意义（P<005）。前哨淋巴结2～5个、肿瘤分期为T2～T3期的患者更容易发生腋窝NSLN转移。多因素Logistic回归分析显示,肿瘤分期为T2～T3期、前哨淋巴结数≤5个是患者腋窝NSLN转移的独立危险因素。结论仅有1个前哨淋巴结转移的乳腺癌患者总体腋窝NSLN转移率为224%,肿瘤T分期和前哨淋巴结数为腋窝NSLN转移的影响因素,在对仅1个前哨淋巴结阳性的乳腺癌患者豁免ALND时应重点考虑。     

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.     

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。     

Pathologic examination of sentinel lymph nodes in breast cancer.

Lymphatic mapping with selective sentinel lymphadenectomy allows accurate pathologic examination of the nodes most likely to contain macro- or micrometastastic disease for staging and proper adjuvant chemotherapy. The hypothesis of SLN biopsies was histopathologically validated by Turner et al that if the node is tumor free by H&E and immunohistochemistry, the probability of non-SLN involvement is less than 0.1%. Giuliano et al and Veronesi et al reported that detection of metastases in SLNs by frozen section technique is 89% and 64%, respectively. At MCC, frozen section evaluation of SLN is not performed because of its potential loss of micrometastasis in the cryostat, freezing artifacts, sampling error, and perhaps radioactive contamination. Intraoperative detection of macro- or micrometastasis is critical because it enables conversion of patients with positive SLN to CLND in one surgical setting more cost-effectively. IIC of the lymph nodes has been used routinely in the diagnosis of hematologic malignancies and also in breast cancer as a useful method in many series. In the author's experience, IIC by Diff-Quik stain converted 100% of grossly positive and suspicious SLNs and 22% of grossly negative SLNs. The significance of detecting micrometastases in axillary lymph nodes using immunohistochemical techniques has been reported in many series. At the MCC, routine use of CKI on paraffin sections of grossly negative SLNs enabled the upstaging of 10.6% of patients from N0 to N1. Recent addition of intraoperative rapid CKI as an adjunct to complement Diff-Quik stain has proven to be more sensitive in detecting micrometastases than using Diff-Quik stain alone. IIC technique using either Diff-Quik stain or CKI requires intensive training and experience to avoid potential pitfalls and errors in interpretation. Evaluation of SLN should use methods that enhance the ability to detect micrometastasis, however, in a cost-effective manner. The cost-effectiveness of IIC by Diff-Quik stain is incomparable with frozen section evaluation. The added cost of routine immunohistochemical stain and perhaps multiple levels of H&E stain should be offset by the decreased costs of IIC and clinically by treating most patients in the outpatient settings. In summary, IIC by Diff-Quik stain is simple, rapid, and has excellent diagnostic accuracy in grossly positive and suspicious SLNs allowing cost-effective, immediate CLND. IIC by CKI is an extremely useful ancillary technique that complements Diff-Quik stain in detecting micrometastases particularly in low grade ductal or lobular carcinoma and low tumor cell volume. Appropriate combined use of both stains may lead to intraoperative nodal staging and cost-effective CLND. SLN mapping technology at MCC using IIC in conjunction with serial sections, entire tissue submission, routine use of CKI, and multiple levels of the SLN have led us to uncover micrometastasis in high-risk, traditionally node-negative patients. These results have encouraged investigators to pursue even more sensitive techniques to detect micrometastases, including molecular biology techniques such as RT-PCR. Experienced cytopathologists and active cytopathology services are required to avoid potential pitfalls in performing and interpreting IIC. More long-term follow-up and prospective trials are needed to determine the prognostic significance of upstaging by ancillary techniques, which may lead to a revision of the current TNM staging system.     

Clinical impact of false-negative sentinel lymph nodes in breast cancer

Aims

To evaluate the incidence of false-negative (FN) sentinel lymph node (SLN) cases, their correlation with a series of clinico-pathologic parameters and their impact on adjuvant treatment indications and on clinical axillary relapse in the setting of a multicentric clinical trial comparing SLN biopsy with axillary lymph node dissection (ALND).

Methods

A series of 697 patients with primary breast cancer ≤ 3 cm were randomized to SLN biopsy associated with ALND (ALND arm) or to SLN biopsy followed by ALND only if the SLN was metastatic (SLN arm). The FN SLN rate was assessed in the ALND arm. A series of 11 clinico-pathological parameters were tested for a possible association with FN results. The indications for adjuvant treatments were evaluated by considering both the FN nodal stages, as indicated by the SLN, and the true positive axillary status, as indicated by completion ALND. The occurrence of clinically evident axillary recurrences was evaluated in the two arms.

Results

The FN rate was 16.7%. Of the clinico-pathologic parameters tested, only a tumour size ≤ 2 cm and the presence of a single metastatic axillary node was significantly associated with a risk of FN (p = 0.033 and p = 0.018, respectively). The FN SLN would have led to different adjuvant therapy indications in 12/18 cases. At 56 months, no clinically evident axillary nodal recurrences were present in the ALND arm patients, whereas one case of axillary recurrence was detected in the SLN arm patients.

Conclusions

FN SLN biopsy is not uncommon, especially in the presence of a small primary tumour with a single nodal metastasis. An FN finding can lead to less than optimal adjuvant treatment. However, the clinical impact of FN in terms of axillary recurrence at 56 months was minimal.     

乳腺癌前哨淋巴结和非前哨淋巴结转移的影响因素分析

目的 探讨影响乳腺癌前哨淋巴结和非前哨淋巴结转移的相关因素.方法 回顾性分析2010年7月至2011年8月收治的、行前哨淋巴活检的283例女性乳腺癌患者的临床资料.结果 单因素分析结果显示,患者年龄、是否绝经、肿瘤大小、病理类型和脉管瘤栓均与前哨淋巴结转移(SLNM)有关(均P＜0.05);年龄、恶性肿瘤家族史、绝经情况、局部切除术、示踪技术、前哨淋巴结阳性、肿瘤大小、病理类型、分化程度、雌激素受体(ER)阳性、孕激素受体阳性、人表皮生长因子受体2阳性数目、脉管瘤栓和Ki-67≥15％等均与非前哨淋巴结转移无关(均P＞0.05).Logistic回归分析结果显示,患者年龄、肿瘤大小和脉管瘤栓均与SLNM有关(均P＜0.05).结论 患者年龄、肿瘤大小和脉管瘤栓是影响SLNM的独立因素,其中年龄是保护因素.而病理类型、病理分级和ER状态是否与SLNM有关存在争议.     

Molecular analysis of breast sentinel lymph nodes

Lymphatic mapping and sentinel lymph node (SLN) biopsy have become the standard of care for staging the axilla in patients with invasive breast cancer. Current histologic methods for SLN evaluation have limitations, including subjectivity, limited sensitivity, and lack of standardization. The discovery of molecular markers to detect metastases has been reported over the last 2 decades. The authors review the historical development of these markers and the clinical use of one of the molecular platforms in 478 patients at their institution. Controversies and future directions are discussed.