乳癌前哨淋巴结中mammaglobin检测的临床意义

目的 探讨乳癌前哨淋巴结中mammaglobin检测的临床意义。方法 32例乳癌患者术中注射亚甲蓝定们前哨淋巴结（SLN），巢式RT－PCR法检测腋淋巴结中mammaglobin mRNA的表达。结果 SLN定位成功率为93.8%(30/32),SLN与非SLN组微转移检出率有显著统计学差异（P＜0.01）；在常规病检阴性的淋巴结中，巢式RT－PCR法的微转移的检出率为14.4%（36／263）。结论 mammaglo-bin巢式RT－PCR法是较常规病理检查更为敏感的检出淋巴结转移的方法。联合SLN定位和巢式RT－PCR的检测，可明显提高乳癌腋淋巴结微转移的检出效率。     

乳腺癌前哨淋巴结微转移的研究

目的：提高乳腺癌前哨淋巴结（SLN）病理诊断的准确性，为手术彻底切除肿瘤提供依据。方法：应用亚甲蓝生物染色的方法确定60例Ⅰ、Ⅱ期乳腺癌SLN并活检，44（73．3％）例SLN取材成功。每一枚SLN均进行冰冻病理切片、石蜡病理和角蛋白Keratinl9（CK-19）逆转录聚合酶链反应（RT—PCR）检测。结果：44例SLN冰冻病理切片、石蜡病理切片和CK-19诊断的灵敏度和特异度分别是77．8％和100．0％、88．9％和100．0％、100．0％和82．9％，诊断符合率分别为95．5％、97．7％和86．4％，诊断指数分别为0．778、0．889和0．829。结论：CK-19检测可进一步提高乳腺癌SLN微转移的检出率，提高SLN活检的准确性。但CK-19检测与冰冻病理病理检查联合应用可提高诊断的准确率和临床的可操作性。     

Sentinel lymph node biopsy in breast cancer. Experience of the Rome Breast Cancer Study Group

We report our multicentric experience with sentinel lymph node biopsy for breast cancer patients. Patients with breast cancer operated on from January 1999 to March 2005 in 6 different institutions in the Rome area were retrospectively reviewed. All patients gave written informed consent. 1440 consecutive patients were analysed, with a median age of 59 years (range: 33-81) and a median tumour diameter of 1.3 cm (range: 0.1-5). Patients underwent lymphatic mapping with Tc99 nanocolloid (N = 701; 49%), with Evans Blue (N = 70; 5%), or with a combined injection (N = 669, 46%). The majority of patients were mapped with an intradermal or subdermal injection (N = 1193; 84%), while an intraparenchymal or peritumoral injection was used in 41 (3%) and 206 patients (13%), respectively. Sentinel lymph nodes were identified in 1374/1440 cases (95.4%), and 2075 sentinel lymph nodes were analysed (average 1.5/patient). A total of 9305 additional non-sentinel lymph-nodes were removed (median 6/patient). Correlations between sentinel lymph nodes and final lymph node status were found in 1355/1374 cases (98.6%). There were 19 false-negative cases (5%). Lymph node metastases were diagnosed in 325 patients (24%). In this group, micrometastases (< 2 mm in diameter) were diagnosed in 103 cases (7.6%). Additionally, isolated tumour cells were reported in 61 patients (4,5%). In positive cases, additional metastases in non-sentinel lymph-nodes were identified in 117/325 cases after axillary dissection (36%). Axillary dissection was avoided in 745/1440 patients (52%). At a median follow-up of 36 months, only 1 axillary recurrence has been reported. Sentinel lymph node biopsy improves staging in women with breast cancer because it is accurate and reproducible, and allows detection of micrometastases and isolated tumour cells that would otherwise be missed. Our multicentric study confirms that this is the preferred axillary staging procedure in women with breast cancer.     

Endoscopic sentinel node detection with a gamma probe combined with minimally invasive axillary lymph node dissection: a preliminary study.

OBJECTIVE: To investigate the efficacy of videoendoscopic axillary lymph node dissection combined with endoscopic sentinel node detection by gamma probe and preoperative sentinel node imaging. DESIGN: Open study. SETTING: University hospital, Germany. SUBJECTS: Four patients with breast cancer. INTERVENTION: Injection of 99mTc-nanocolloid around the tumour. RESULTS: In three patients axillary sentinel nodes were detected both before and after operation. In the remaining one it was not found. In two patients the minimally invasive approach had to be converted to conventional open surgery because of anatomical restrictions. CONCLUSION: We describe a new approach that uses a minimally invasive technique and endoscopic radioguided sentinel node biopsy in patients with breast cancer. The results of this preliminary study warrant further investigation.     

吲哚菁绿与纳米碳在乳腺癌前哨淋巴结活检中的对比研究

目的:比较吲哚菁绿(ICG)、纳米碳混悬注射液在乳腺癌前哨淋巴结(SLN)示踪中的应用效果。方法:选择2013年11月—2016年7月收治乳腺癌行前哨淋巴结活检(SLNB)的患者136例,其中以ICG为示踪剂者60例(ICG组),以纳米碳混悬注射液为示踪剂者76例(纳米碳组)。比较两组的相关指标。结果:两组基本临床资料差异无统计学意义(均P0.05);ICG组与纳米碳组SLN的检出率(96.67%vs.100%)、灵敏度(89.47%vs.95.83%)、假阴性率(10.53%vs.4.17%)、准确率(93.33%vs.98.68%),组间差异均无统计学意义(均P0.05);ICG组较纳米碳组SLN检出数目少(3.17枚vs.3.92枚,P=0.000),但检出时间短(25.72 min vs.49.29 min,P=0.000);年龄、体质量指数(BMI)并不影响两种方法的SLN检出率及SLNB准确率(均P0.05)。结论:ICG与纳米碳混悬注射液示踪乳腺癌SLN具有相似的效能,并且均操作简便,便于推广实施。     

Predictors of positive axillary lymph nodes after sentinel lymph node biopsy in breast cancer.

OBJECTIVE: The purpose of this study was to determine the factors that predict the presence of metastasis in nonsentinel lymph nodes (SLN) when the SLN is positive. METHODS: A prospective database was analyzed and included patients who underwent SLN biopsy for invasive breast cancer from July 1997 to August 2000 (n = 442). One hundred (22.6%) patients had one or more positive SLNs, and were analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: Of the 100 patients with a positive SLN, 40 patients (40%) had additional metastasis in non-SLNs. The only significant variables that predicted non-SLN metastasis were tumor lymphovascular invasion (P = 0.004), extranodal extension (P < 0.001), and increasing size of the metastasis within the SLN (P = 0.011). In analyzing just those patients who had lymphovascular invasion, extranodal extension, and a SLN metastasis > 2mm, 92% were found to have additional positive nodes. CONCLUSIONS: In patients with invasive breast cancer and a positive sentinel lymph node, lymphovascular invasion, extranodal extension, and increasing size of the metastasis all significantly increase the frequency of additional positive nodes.     

前哨淋巴结阳性乳腺癌非前哨淋巴结转移的情况分析

目的探讨前哨淋巴结（SLN）阳性乳腺癌患者的临床病理特征与非前哨淋巴结（NSLN）转移的关系。 方法回顾性分析2010年1月至2016年1月中山大学附属第一医院500例行前哨淋巴结活检（SLNB）的临床分期为T_1-2N₀M₀期乳腺癌患者资料,其中病理检查确诊SLN阳性、随后行腋窝淋巴结清扫（ALND）的乳腺癌患者共89例,总结其临床、病理因素的特征及其对腋窝NSLN转移的影响因素进行单因素及多因素Logistic分析。 结果SLN阳性率为17.8%（89/500）,49.4%（44/89）出现NSLN转移。单因素分析显示,NSLN转移与原发肿瘤分期、脉管浸润、SLN阳性数、SLN阳性率相关（χ²=4.062、36.084、7.003、10.889,P=0.044、<0.001、0.030、0.004）。进一步多因素Logistic回归分析显示,脉管浸润、SLN阳性率是NSLN转移的独立预测因子（OR=46.142,95%CI：11.821~258.472,P<0.000 1;OR=10.482,95%CI：2.564~51.312,P=0.002）。 结论SLN阳性的乳腺癌患者,其原发肿瘤分期、肿瘤是否多发、脉管浸润、SLN阳性数、SLN转移率与腋窝NSLN转移相关。其中,脉管浸润及SLN阳性率≥0.5是SLN阳性乳腺癌患者腋窝NSLN转移的独立预测因子。     

乳腺癌新辅助化疗后前哨淋巴结分析的研究进展

腋窝淋巴结清扫术（ALND）作为评估腋窝淋巴结状态的金标准常应用于乳腺癌手术中。但随着医疗技术的发展,在保证生存率及尽量减少复发的前提下,临床上越来越重视患者的生存质量。ALND也因其会造成手臂淋巴水肿、肩部功能障碍等副作用,使用率逐渐下降,取而代之的是创伤更小、使患者的生活质量更好的前哨淋巴结活检术（SLNB）,SLNB也是早期浸润性乳腺癌患者腋窝淋巴结处理的标准方式。新辅助化疗（NAC）作为全身系统治疗重要组成部分,不仅可以缩小肿瘤,增加手术机会,还可以增加保乳率,为更多患者带来临床获益。但NAC后的SLNB因受NAC对淋巴管等作用的影响,存在检出率低及假阴性率（FNR）高的问题,这也使NAC后行SLNB备受争议,如何使更多符合标准的乳腺癌人群豁免ALND获得临床获益是亟待解决的临床问题。目前已有多种技术方法尝试用于提高乳腺癌NAC后SLNB检出率及降低FNR。相比单一示踪剂,联合蓝染料及核素两种传统示踪剂或结合纳米碳混悬液、吲哚菁绿、微泡超声造影、超顺磁氧化铁等新型示踪剂,或是采用纳米颗粒辅助腋窝分期对前哨淋巴结进行示踪,可显著提高SLNB的检出率。多项大型前瞻性试验证明,保证≥3枚前哨淋巴结被切除可显著降低SLNB的FNR;靶向ALND作为SLNB的补充,通过在术前对阳性淋巴结进行标记定位可实现精准切除淋巴结,利用雷达反射器、碳文身、放射性粒子、磁性粒子、术中超声等进行定位可进一步提高其准确性。另外,有研究提出结合影像检查如腋窝超声图像、CT淋巴成像等,能清楚显示淋巴结及其周围淋巴管解剖结构,增加临床医师的把握度,进一步提高检出率,降低FNR,但暂未得到大型试验数据证实。笔者对目前NAC后的前哨淋巴结分析的相关研究进行系统总结,旨在为临床提供思路和方向,关于在临床上具体如何抉择能使更多患者获益未来仍需大量研究来验证。     

Imprint cytology versus frozen section: intraoperative analysis of sentinel lymph nodes in breast cancer

Background: Intraoperative analysis of the sentinel node status in breast cancer adds the benefit of proceeding to axillary dissection at the same time as the primary breast operation, without the need for a second trip to theatre. However, the method of intra­operative analysis must be both rapid and accurate for use in this setting. Methods: A prospective series of 20 consecutive patients in one hospital who underwent sentinel node biopsy was performed. Intraoperative evaluation by imprint cytology and frozen section was compared with the final histopathological results. The time taken for both procedures was recorded. Results: A total of 21 sentinel node procedures was performed. The sentinel node was found in 20 procedures (95%). The average time to perform intraoperative pathological analysis was 17 min (range: 5?35 min). Of the eight positive sentinel nodes, five were positive on imprint cytology alone and five were positive on frozen section alone (62.5% accuracy). The statistical false negative rate was 18.8% and the ‘false reassurance rate’ (patients with an initially negative node that was subsequently positive on formal histology who required a second trip to theatre for axillary dissection) was 37.5%. All patients with a negative sentinel node had a negative axilla. Conclusions: Intraoperative analysis of sentinel lymph nodes in breast cancer can be performed quickly. Imprint cytology and frozen section show comparable accuracy in predicting sentinel node status.     

Arm morbidity following sentinel lymph node biopsy or axillary lymph node dissection: a study from the Danish Breast Cancer Cooperative Group

BACKGROUND: Sentinel lymph node biopsy was implemented in the treatment of early breast cancer with the aim of reducing shoulder and arm morbidity. Relatively few prospective studies have been published where the morbidity was assessed by clinical examination. Very few studies have examined the impact on shoulder mobility of node positive patients having a secondary axillary dissection because of the findings of metastases postoperatively. AIM: We aimed to investigate the objective and subjective arm morbidity in node negative and node positive patients. METHODS AND MATERIALS: In a prospective study, 395 patients with tumors less than 4 cm, were included. Patients were recruited from seven Danish breast cancer clinics. Both subjective and objective arm and shoulder morbidity were measured before, 6 and 18 months after the operation. RESULTS: Comparing node negative patients having a sentinel lymph node biopsy with node negative patients having a lymph node dissection of levels I and II of the axilla, we found significant increase in arm volume among the patients who had an axillary dissection. Only minor, but significant, differences in shoulder mobility were observed comparing the two groups of node negative patients. Highly significant difference was found comparing sensibility. Comparing the morbidity in node positive patients who had a one-step axillary dissection with patients having a two-step procedure (sentinel lymph node biopsy followed by delayed axillary dissection) revealed no difference in objective or subjective arm morbidity. CONCLUSION: Node negative patients operated with sentinel lymph node biopsy have less arm morbidity compared with node negative patients operated with axillary lymph node dissection. Node positive patients who had a secondary axillary lymph node dissection after sentinel lymph node biopsy had no difference in either objective or subjective morbidity compared with node positive patients having a one-step axillary dissection.     

Prognostic value of number of removed lymph nodes, number of involved lymph nodes, and lymph node ratio in 7502 breast cancer patients enrolled onto trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)

Purpose

The number of removed axillary lymph nodes and the ratio of involved to removed lymph nodes are described as independent prognostic factors beside the absolute number of involved lymph nodes in breast cancer patients. The correlation between these factors and prognosis were investigated in trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG).

Methods

This retrospective analysis is based on the data of 7052 patients with endocrine-responsive breast cancer who were randomized in four trials of the ABCSG in the years 1990?C2006 and underwent axillary lymph node dissection. The prognostic value of number of removed nodes (NRN), number of involved nodes (NIN), and ratio of involved to removed nodes (lymph node ratio, LNR) concerning recurrence-free survival and overall survival was analyzed.

Results

A total of 2718 patients had node-positive disease. No correlation was found between NRN and prognosis. Increasing NIN and LNR were significantly associated with worse recurrence-free survival and overall survival in univariate and multivariate analyses (P?<?.001). Only in the subgroup of patients with one to three positive lymph nodes and treated with mastectomy (n?=?728) was LNR an additional prognostic factor in univariate and multivariate analyses.

Conclusions

For breast cancer patients stringently medicated in the framework of prospective adjuvant clinical trials and requiring a mandatory minimum of removed nodes, NRN does not influence prognosis, and LNR is not superior to NIN as prognostic factor. In patients with one to three positive lymph nodes and mastectomy, LNR could play a role as an additional prognostic factor.     

Subpleural injection of tracer improves detection of mediastinal sentinel lymph nodes in non-small cell lung cancer.

BACKGROUND: The advantages and disadvantages of various tracer injection protocols for sentinel lymph node (SLN) mapping have been extensively discussed in relation to breast and gastric cancer. But no such discussion has taken place in relation to SLN mapping in non-small cell lung cancer. We therefore studied the effect of two tracer injection protocols on SLN mapping in patients with non-small cell lung cancer; of particular interest was the relationship between subpleural tracer injection and identification of mediastinal SLNs. METHODS: A quadrant injection group (n=49) received 1.6 ml of ferucarbotran by peritumoral quadrant injection after thoracotomy. In the subpleural injection group, the same amount of ferucarbotran was injected into the peritumoral quadrants plus the subpleural region (n=27). SLNs were then detected intraoperatively by measuring the magnetic force within lymph nodes using a hand-held magnetometer. After completing the SLN mapping, lobectomy and hilar and mediastinal lymph node dissection was performed. RESULTS: The incidence of mediastinal SLNs was significantly higher in the subpleural injection group (45.4%) than in the quadrant injection group (14.6%) (p=0.007). Moreover, nominal logistic regression analysis revealed subpleural injection to be a significant independent factor contributing to detection of mediastinal SLNs (p=0.024, odds ratio 5.26). In the quadrant injection group, mediastinal lymph node metastasis was detected in two patients thought to have nonmetastatic parenchymal SLNs. By contrast, there were no false-negative cases in the subpleural injection group. CONCLUSION: Subpleural tracer injection significantly improves detection of mediastinal SLNs in non-small cell lung cancer.