Clinical considerations in breast cancer sentinel lymph node mapping: A moffitt review

Lymphatic mapping redefined the clinical significance of axillary lymph nodes in the treatment of breast cancer. Current literature supports the concept that any patient diagnosed with invasive breast cancer should in fact have their sentinel lymph nodes evaluated. However, there are many cases of “specialsituations in lymphatic mapping”. These special situations mark an important point that should be considered: When and who should undergo lymphatic mapping? A summary of these considerations/cases will be the focus of this report.     

Multidisciplinary approach to selective sentinel lymph node mapping in breast cancer

Although the role of axillary lymph node dissection is controversial with respect to survival benefits, its role as a staging procedure has been well established since nodal involvement is the most reliable prognostic indicator for patients with breast cancer. Selective sentinel lymph node (SLN) dissection is gaining acceptance as a useful staging procedure because it is minimally invasive and spares approximately 70-80% of the patients a more extensive axillary lymph node dissection. The evolving techniques for selective SLN dissection using blue dye and radiotracer methods are reviewed in this article. Based on the classic definition of the breast lymphatic drainage and recently published articles addressing the issue of peritumoral and intradermal injections, a possible new and simplified approach using intradermal injection may identify the axillary SLN more quickly and reliably. This article emphasizes the importance of a multidisciplinary approach in the identification of SLNs by preoperative lymphoscintigraphy performed by expert nuclear medicine physicians, the intraoperative mapping and harvesting of SLNs by well trained surgeons and the meticulous examination of SLNs by experienced pathologists. Therefore, to achieve the highest rate of accuracy regarding SLN status, it is imperative that a multidisciplinary team with close communication and cooperation be formed. The clinical significance of SLNs will be determined by results from follow-up and clinical trials.     

新型荧光示踪剂在乳腺癌前哨淋巴结活检术中的应用研究

背景与目的：吲哚菁绿（indocyanine green,ICG）与利妥昔单抗（rituximab,Rit）偶联可使ICG在淋巴结显像中具有靶向性。探讨ICG-Rit用于乳腺癌前哨淋巴结活检（sentinel lymph node biopsy,SLNB）的可行性。方法：入组山东省肿瘤防治研究院（山东省肿瘤医院）乳腺病中心96例原发性乳腺癌患者（100例次SLNB）。ICG与Rit质量比为93.75 μg∶375.00 μg。术前行ICG-Rit、联合示踪剂（亚甲蓝及核素示踪剂）乳房注射,联合法行SLNB,对检出淋巴结进行荧光显像检测,记录荧光显像淋巴结及灰度值,分析ICG-Rit淋巴结显像情况并评价对比联合法的一致性。观察患者过敏反应并检测术后嗜酸性粒细胞计数。结果：ICG-Rit病例显像率为97.0%（97/100）。ICG-Rit显像前哨淋巴结（sentinel lymph node,SLN）的均数为2.44,中位数为2;低于核素法检出SLN的均数（2.80）和中位数（3）。ICG-Rit对比联合法SLNB的准确率为97.0%（97/100）,灵敏度为96.2%（25/26）,假阴性率为3.8%（1/26）,kappa值为0.973（P＜0.001）。显像淋巴结灰度值最高254,显像淋巴结灰度值集中在220~254,＜220者术中荧光不易察觉,缺乏连续性。入组患者术前未见过敏反应,术后嗜酸性粒细胞计数未增高。结论：ICG-Rit能够减少对非SLN（non-SLN,n-SLN）的显像。对比联合法,准确率和符合率高,安全性良好。     

乳腺癌前哨淋巴结活检示踪剂研究进展

传统的示踪剂核素和蓝染料存在一定缺点。近年来国内外学者试图研发一款功能优化的新型示踪剂,有助于前哨淋巴结活检术(sentinel lymph node biopsy,SLNB)的推广。吲哚菁绿价格较低,使用安全,但穿透力有限(1 cm)且缺乏靶向性。超声造影剂可实时动态地观察显影淋巴管和淋巴结,但成功率和准确性相对较低。超顺磁氧化铁作为前哨淋巴结示踪剂,操作方便,可避免医源性核素污染,具有良好的应用前景。     

Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer

BACKGROUND: Sentinel lymph node biopsy using a vital dye is a convenient and safe method to assess lymph node status in breast cancer. However, intensive training is necessary to obtain a satisfactory detection rate and to avoid false-negative results. This paper presents a novel method using indocyanine green fluorescence imaging to detect sentinel lymph nodes. METHODS: Fluorescence images were obtained using a charge coupled device camera with a cut filter as the detector, and light emitting diodes at 760 nm as the light source. When indocyanine green was injected around the areola, subcutaneous lymphatic channels draining from the areola to the axilla were visible by fluorescence within a few minutes. The sentinel lymph node was then dissected by fluorescence navigation. RESULTS: Sentinel lymph node biopsy using the present method was performed on eighteen patients. Subcutaneous lymphatics were detectable by fluorescence in all patients, and sentinel nodes were successfully identified in 17 of 18 cases (detection rate:94%). It was possible to detect the lymphatic channels and nodes receiving indocyanine green with higher sensitivity by the fluorescence signal than by the green color. CONCLUSION: Sentinel node biopsy guided by indocyanine green fluorescence imaging is a promising technique for further clinical exploration.     

早期乳腺癌前哨淋巴结活检的前沿进展

医学影像技术的飞速发展提高了早期乳腺癌腋窝淋巴结影像学诊断的能力,能够检测到腋窝淋巴结更早、更小的转移灶,通过影像学引导下穿刺活检明确淋巴结的转移状况,从而为患者提供更完善的术前腋窝分期。对于术前超声影像学检查为腋窝淋巴结阴性的患者是否可以避免术中腋窝前哨淋巴结活检,目前有两项大型临床试验正在进行中。山东大学附属山东省肿瘤医院乳腺病中心通过微泡超声造影显像技术引导腋窝前哨淋巴结术前穿刺活检,正在探索一种高效、准确和超微创的腋窝前哨淋巴结活检技术。术前影像学检查大大提高了临床腋窝淋巴结阳性患者的检出率,但也让一部分患者失去了通过腋窝前哨淋巴结活检替代腋窝淋巴结清扫的机会,对临床查体淋巴结阴性但超声发现可疑淋巴结并通过穿刺活检确诊转移的患者是否适合前哨淋巴结活检,本文也进行了相关的探讨和研究。另外,对内乳前哨淋巴结活检的相关研究结果进行了汇总。     

乳晕下注射示踪剂行前哨淋巴结活检的可行性

目的探讨乳晕下联合注射核素和美蓝行前哨淋巴结活检的可行性。方法选择2004年10月至2007年2月早期乳腺癌患者195例，将患者抽签随机分为两组：一组将示踪剂注射在肿瘤周围（肿瘤周围组）；另一组将示踪剂注射在乳晕下（乳晕下组）。对所有患者均先行前哨淋巴结活检，再行腋窝淋巴结清扫。将所有的前哨淋巴结和非前哨淋巴结均进行常规切片和HE染色检查，对常规病理检查阴性的前哨淋巴结行多层切片和免疫组化检查。结果全组195例，肿瘤周围组98例，乳晕下组97例。肿瘤周围组与乳晕下组前哨淋巴结活检成功率分别为92．9％和97．9％（P=0．17）。经常规病理检查或多层切片加免疫组化检查后，肿瘤周围组有25例SLN阳性，乳晕下组29例SLN阳性。经腋窝淋巴结清扫后，肿瘤周围组有2例SLN为假阴性，假阴性率为7．4％（2／27），乳晕下组有3例假阴性，假阴性率为9．4％（3／32），两组间差异无统计学意义。肿瘤周围组和乳晕下组对腋窝淋巴结预测的准确度分别为97．8％和96．8％，灵敏度分别为92．6％和90．6％，差异均无统计学意义。结论乳晕下注射两种示踪剂行前哨淋巴结活检与肿瘤周围注射相比具有同样预测腋窝淋巴结状况的准确性，同时能避免肿瘤周围注射存在的缺点，是较佳的注射途径。     

Controversies in sentinel node biopsy for breast cancer

Sentinel node biopsy for breast cancer patients has recently been applied as a less invasive, highly accurate alternative to axillary lymph node dissection. Numerous studies have shown that sentinel nodes accurately diagnose axillary staging. However, many problems remain to be answered and must be addressed before sentinel node biopsy becomes the standard surgical procedure for patients with breast cancer. We reviewed and discussed here three of these problems; axillary sampling as an alternative to sentinel node biopsy, dye method vs. combination of dye and radiocolloid for sentinel node biopsy, and intraoperative sentinel node examination. Further investigation will continue to be necessary as we learn how to better provide procedure of sentinel node biopsy.     

中国乳腺癌前哨淋巴结活检现状调查研究

背景与目的：前哨淋巴结活检（sentinel lymph node biopsy,SLNB）已经成为乳腺癌临床腋窝淋巴结阴性患者的标准腋窝分期方案。由中国抗癌协会乳腺癌专业委员会发起的SLNB调查研究,旨在了解中国大型医院乳腺癌SLNB的开展现状。方法：在全国范围内纳入2017年手术量大于200例的医院,共110家医院完成问卷调查。调查问卷包括SLNB的开展现状、免除腋窝清扫及新辅助化疗（neoadjuvant chemotherapy,NAC）中SLNB的应用等热点问题。采用χ ² 检验、Fisher确切概率法或Kolmogorov-Smirnov检验对数据进行分析。结果：参与调研的110家医院均开展了SLNB,其中,85家（77.27%）医院对超过50%的临床腋窝淋巴结阴性（cN ₀ ）乳腺癌患者常规进行SLNB。肿瘤专科医院（χ ² =5.62,P=0.018）、保乳手术（breast-conserving surgery,BCS）量较大的医院（D=0.33,P=0.032）开展SLNB的比例更高。大部分医院（93/110,84.55%）未开展内乳SLNB。最常用的示踪方法为染料（主要是亚甲蓝,69/110,62.73%）,仅14.55%（16/110）的医院使用核素联合染料双示踪法。几乎所有的医院（107/110,97.27%）均采用术中快速冰冻切片对前哨淋巴结（sentinel lymph node,SLN）进行病理学诊断。对于cN ₀ 、SLN 1~2枚转移的BCS患者,大部分医院（61/110,55.45%）仅对少于10%的该类患者免除后续腋窝淋巴结清扫（axillary lymph node dissection,ALND）。对于cN ₀ 、SLN 1~2枚转移的全乳切除患者,84家（76.36%）医院对少于10%的此类患者免除后续ALND。对于接受NAC的患者,50家（45.45%）医院在NAC后进行SLNB,60家（54.55%）医院在NAC前进行SLNB。行NAC较多的医院（χ ² =4.365,P=0.037）、在NAC期间常规使用磁共振成像（magnetic resonance imaging,MRI）评估的医院（χ ² =10.967,P=0.004）,更倾向于在NAC后行SLNB。结论：尽管示踪剂的规范应用尚有待改进,早期乳腺癌患者的SLNB已经成为中国评估腋窝状态的标准方式。对于SLN转移负荷较低的患者,国内学者对于免于腋窝清扫仍较为保守。接受NAC的患者,SLNB的应用时机仍存在争议。     

乳腺癌前哨淋巴结活检术新型示踪剂的研究进展

随着前哨淋巴结活检术成为临床腋窝淋巴结阴性的早期乳腺癌患者的标准处理模式,关于活检示踪剂的研究成为乳腺癌研究的热点之一。目前,临床上应用较多的示踪剂包括蓝染料、核素及二者的结合,但这两种示踪剂存在的某些不足导致发达国家仅有60%的患者进行前哨淋巴结活检,中国仅占约5%,其他发展中国家更少。近年来,各种新型示踪剂的研究层出不穷,如吲哚菁绿、使用微气泡的对比增强超声和超顺磁性氧化铁颗粒等。该文回顾了这三种物质的特性及作为示踪剂的相关研究,这些新型示踪技术仍处于初级研究阶段,有待于进一步实验以便临床应用。     

乳腺癌前哨淋巴结微小转移的检测

前哨淋巴结(SLN)可以反映腋窝淋巴结的转移状况,检测SLN微小转移可以筛查出常规病理检查阴性中的高危患者,从而使治疗更加有的放矢。检测微小转移的方法有多层面切片、免疫组化染色和逆转录-聚合酶链反应(RT-PCR)。不同方法微小转移的检出率不同,其临床意义目前尚无定论；对于SLN有微小转移者,是否应清扫腋窝也在研究中。     

原发性乳腺癌前哨淋巴结转移的影响因素分析

目的 探讨影响原发性乳腺癌前哨淋巴结转移（SLNM）的相关因素。方法 回顾性分析2008年1月至2014年12月北京市顺义区妇幼保健院乳腺中心收治的原发性乳腺癌且行前哨淋巴结活检的264例女性患者的临床病例资料。分析SLNM与临床病理特征的关系。结果 264例乳腺癌患者中,发生SLNM 59例。单因素分析显示,肿瘤大小、ER表达、HER-2表达均与SLNM有关（P＜0.05）。非条件Logistic回归分析显示,肿瘤大小及HER 2表达是影响SLNM的独立因素（均P＜0.05）。结论 肿瘤大小和HER-2表达是影响乳腺癌SLNM的独立因素,其他临床病理特征与SLNM的关系有待进一步研究。     

Lymphatic mapping and sentinel lymph node biopsy in the patients with breast cancer

Axillary lymph node dissection (ALND) is always standard part for a variety of surgical treatments of breast cancer. Knowledge of the status of axillary nodes presents important information for staging and prognosis, but it remains controversial that ALND provides local control of disease and offer survivalbenefit. Some authors have questioned the wisdom of continuing to do ALND, when the risk of axillary metastasis in the early case is small, and the postoperative complications are usuall…     

Isolated retromammary lymph node metastasis of breast cancer without axillary lymph node involvement: a case report with a false-negative sentinel lymph node biopsy

A 54-year-old woman visited our hospital with a palpable tumor in her left breast, which was diagnosed as invasive ductal carcinoma. Breast-conserving surgery was performed, in association with a sentinel lymph node (SLN) biopsy and back-up dissection of the axillary lymph nodes. One dyed axillary lymph node with high radioactivity was defined as an SLN, and intraoperative frozen-section analysis of the SLN was negative for metastasis. The final pathological diagnosis of the tumor was invasive ductal carcinoma, and one small lymph node, located in the retromammary space, just under the tumor, was positive for metastasis. The backup axillary lymph nodes were not metastatic. This patient was diagnosed false-negative by SLN biopsy, despite being positive for retroMLN metastasis. It should be recognized that retroMLNs are difficult to detect preoperatively, or intra-operatively, using dye or radiocolloid, if they are located in the post-tumoral retro-mammary space. RetroMLNs may be a pitfall in SLN biopsies.     

Breast cancer sentinel lymph node mapping using near infrared guided indocyanine green and indocyanine green--human serum albumin in comparison with gamma emitting radioactive colloid tracer

Aims

Recently, a novel method of using near infrared (NIR) guided indocyanine green (ICG) and ICG conjugated with human serum albumin (ICG:HSA) for sentinel lymph node biopsy (SLNB) of breast cancer patients has shown true potential. The aim of this study was to compare the usefulness of NIR guided ICG and ICG:HSA against the gamma emitting radiocolloid (RC).

Methods

A group of 49 consecutive breast cancer patients underwent SLNB using RC. From this group, the first 28 patients were compared against ICG, while the next 21 patients were compared against ICG:HSA. The number of patients with visible fluorescent path was recorded. Furthermore, the number of SLNs detected by fluorophores percutaneously and total number of intraoperative SLNs detected by fluorophores and/or RC was noted.

Results

NIR guided real time lymphatic flow was observed in 47/49 patients (96%). In all cases except one, SLNs detected by the RC tracer were also detected by their respective fluorophore. Additionally, ICG detected 10 additional SLNs in 8 patients, while 3 additional SLNs were detected by ICG:HSA in 3 patients. Statistical analysis revealed no difference between the number of SLNs detected between ICG versus ICG:HSA and RC versus ICG:HSA. However, a significant statistical difference was observed between RC and ICG (p = 0.0117), as well as between the combined NIR guided and RC method (p = 0.0033).

Conclusions

In conclusion, the use of either ICG or ICG:HSA with RC to obtain SLNB seems to be an effective alternative. Compared to RC alone, the use of ICG:HSA, more so than ICG alone, may provide additional benefits.     

前哨淋巴结活组织检查在早期乳腺癌局部切除术后的临床应用

目的探讨前哨淋巴结活组织检查(SLNB)在早期乳腺癌局部切除术后的临床应用价值。方法回顾性分析2012年3月至2018年11月在山西白求恩医院行SLNB的经肿物切除活组织检查确诊且临床分期为Tis/T1~2N0M0的93例乳腺癌患者,将成功检出前哨淋巴结(SLN)的患者分为SLN阳性组(转移)和SLN阴性组(无转移),通过临床病理资料分析乳腺肿物切除活组织检查后SLN转移及SLN检出数的影响因素。结果93例患者中87例成功检出SLN,检出率为93.5%(87/93),共检出SLN 255枚,每例患者平均检出2.93枚。均进行了术中快速冷冻,共检出11例SLN阳性患者。17例患者行腋窝淋巴结清扫(包括11例SLN阳性和6例SLN未检出患者),14例SLN术后石蜡病理证实为阳性,其中13例为宏转移,1例为微转移;SLN术中冷冻病理诊断的假阴性率为2.1%(3/14)。单因素分析结果显示,组织学分级、是否有脉管内癌栓与局部切除术后乳腺癌SLN转移有关;SLN检出数受体质量指数及染色方法的影响;美兰法联合核素法可提高SLN的检出率(均P<0.05)。多因素分析结果显示,肥胖患者SLN未检出是正常患者的2.651倍(95%CI 1.592~8.194,P=0.010)。结论对乳腺肿物切除术后早期乳腺癌患者采用适当示踪方法,行SLNB具有较高的检出率和临床应用价值。     

前哨淋巴结活检术检测乳腺癌腋窝淋巴结转移的效果评价

区域淋巴结是否转移是影响乳腺癌患者预后的独立因素。临床已证实,对于腋窝淋巴结阴性乳腺癌患者,行常规腋窝淋巴结清除术(axillary lymph node dissection,ALND)无任何治疗意义,而且可引起许多并发症。乳腺癌前哨淋巴结     

Indocyanine green fluorescence imaging for sentinel lymph node detection in colorectal cancer: A systematic review

Indocyanine green fluorescence-imaging (ICG-FI) has emerged as a potential tool for increasing the accuracy of staging of patients with primary colorectal cancer (CRC) through the detection of sentinel lymph nodes (SLNs). Here, we report the results of a systematic review of the available literature in the clinical setting of ex vivo and in vivo ICG-FI for the detection of SLNs in primary colorectal cancer. PubMed, Scopus, and Cochrane literature databases were searched for original articles on the use of ICG in the setting of clinical studies of CRC. Eighty studies were identified and screened, 23 were assessed for eligibility and 10 were included for review. Both ex vivo and in vivo ICG-FI are reported to be feasible for the detection of SLNs in CRC. The reported sensitivity of both techniques remains low, varying from 0% to 100% for the in vivo technique and 57% for the ex vivo technique. ICG-FI has not yet been shown to perform better than the standard blue dye technique. In addition, large variability among reported studies in terms of techniques used (ICG dose, type of injection), type of pathologic analyses performed (HE, IHC, serial section), and definition of positive LN status for sensitivity calculations made them difficult to compare directly. ICG-FI is a promising technique for the detection of SLNs in the setting of CRC but more work needs to be done to clearly define protocols and indications for its use and to test its efficacy in larger patient populations.