核素淋巴显像识别前哨淋巴结在乳腺癌治疗中的应用

目的评价核素淋巴显像和γ探针定位在乳腺癌中确定前哨淋巴结(SLN)的应用价值,验证前哨淋巴结活检替代腋窝淋巴结清除术用于乳腺癌治疗的安全性与价值。方法选择1999年6月至2009年11月本院住院的女性乳腺癌患者206例(体检时腋窝均未扪及肿块),应用99Tcm-DX37～74 MBq或99Tcm-SC74 MBq经皮下注射,行核素淋巴显像后,术中注射专利兰1 ml和(或)术中用γ探针定位并行前哨淋巴结活检,与术中冰冻病理检查结果对照。若术中冰冻发现有前哨淋巴结转移,则行腋窝淋巴结清除术,若前哨淋巴结阴性,则不做腋窝淋巴结清除,术后定期随访。结果 206例乳腺癌术中成功活检SLN204例,成功率为99.0%(204/206)。本组有64例仅行SLN切除,术后病理检查证实64例SLN均阴性,故未行腋窝淋巴结清除,其中仅1例于术后1年时出现腋窝淋巴结转移,其余63例患者在随访期间均未发现腋窝淋巴结转移,也未出现同侧上肢水肿、感觉及活动异常;另140例行腋窝淋巴结清除,其中6例经病理证实SLN阳性但腋窝淋巴结为阴性,134例经病理证实SLN阳性35例,阴性99例,腋窝淋巴结阳性37例,阴性97例。核素淋巴显像和γ探针定位法的灵敏度为94.6%(35/37例),准确率为98.5%(138/140),假阴性为5.4%(2/37)。结论核素淋巴显像和γ探针定位应用于乳腺癌是切实可行和可能的,对预测腋窝淋巴结转移有很大的临床实用价值。如技术方法规范,早期乳腺癌前哨淋巴结活检则能取代常规的腋窝淋巴结清除术,乳腺癌手术上肢并发症的发生率可大大降低。     

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。      

Detection of micrometastases in sentinel lymph nodes of the breast applying monoclonal antibodies AE1/AE3 to pancytokeratins

Sentinel lymph node excision in breast cancer is a minimally invasive diagnostic procedure for accurate staging of the axilla and for avoiding unnecessary axillary dissection. In patients with palpable breast cancer we injected microcolloidal particles of human serum albumin labelled with technetium-99m the day before surgery. The sentinel node was detected intraoperatively with a handheld gammaprobe and then removed. Complete axillary dissection was performed and the nodes inspected by routine histological examination. The axillary lymph node status was correctly predicted by the sentinel node technique in 32 of 33 breast cancer patients. Two cases of micrometastases escaped routine histopathological detection but were identified by immunohistochemical analysis applying the antibody AE1/AE3 to pancytokeratins. Immunohistochemical examination of the sentinel node improves the diagnostic security of patients with breast carcinoma by detection of micrometastases.     

Sentinel node biopsy in breast cancer

Sentinel node biopsy is a promising surgical technique to avoid unnecessary axillary lymph node dissection for breast cancer patients with histologically negative nodes. Several randomized phase III trials in Western countries are underway to assess sentinel node biopsy in cases of breast cancer in comparison with conventional axillary lymph node dissection. Other investigators have also started observational studies in cases when sentinel lymph nodes are proven histologically negative. In Japan, many issues regarding this minimally invasive surgery remain unresolved: optimal procedure, pathologic work-up, radiation exposure, health insurance coverage, and indication for sentinel node biopsy. The current status and problems of sentinel node biopsy in breast cancer are discussed herein.     

The benefits and limitations of sentinel lymph node biopsy

Opinion statement The status of the axilla is the single most important prognostic indicator of overall survival in patients with breast cancer. Staging is based on tumor size and on the presence of lymph node metastases. The number of lymph nodes, although prognostic, no longer impacts treatment options. Sentinel lymph node (SLN) mapping and dissection is a more sensitive and accurate technique for nodal evaluation and has been applied to staging of axillary lymph nodes in patients with breast cancer, providing prognostic information, with less surgical morbidity than with axillary lymph node dissection (ALND). When analyzed by an experienced pathologist with serial sectioning and immunohistochemical evaluation, SLN is the most accurate detection tool used in staging of breast cancer. In many centers that use these staging principles, ALND is no longer performed for histologically negative axillary SLNs. In addition, this technique may also be therapeutic because in most patients, the SLN is the only positive axillary node. SLN biopsy is justified in women with ductal carcinoma in situ who have a high risk of invasive carcinoma, such as those with large tumors, a mass, or high-grade lesions. SLN biopsy is performed in the setting of neoadjuvant chemotherapy and demonstrates accurate evaluation of the axilla in 90% of the cases. Women with locally advanced breast cancer may derive great benefit from a minimally invasive approach to the axilla because the extent of nodal involvement is unlikely to change further treatment. For clinically palpable nodes, ALND should be performed for therapeutic and local control. The use of sentinel node mapping in pregnancy is controversial. Vital blue dye is contraindicated in pregnant patients, although some have used radioactive colloid alone to map this subgroup of patients.     

Sentinel lymph node biopsy as the new standard of care in the surgical treatment for breast cancer

During the recent years, based on the results of validation studies, the sentinel lymph node biopsy has replaced routine axillary dissection as the new standard of care in early breast cancer. The technique represents a minimally invasive, highly accurate method for axillary staging, which could spare approximately 65-70% of patients unnecessary axillary dissection and its related morbidity. Several technical and clinical controversies have been raised during the development of this new technique; the authors review the most important issues, some questions have already been answered and others are still under debate. As far as the technical aspects are concerned, mapping techniques, appropriate surgical training, options for pathological examination of sentinel lymph nodes and the issue of nonaxillary sentinel lymph nodes are discussed. An update on clinical controversies demonstrates that factors such as large tumor size, palpable axillary nodes, multifocality and multicentricity, previous breast and axillary surgery, and pregnancy are no longer regarded as absolute contraindications for sentinel lymph node biopsy. Feasibility, accuracy and timing of sentinel lymph node biopsy in patients undergoing neoadjuvant chemotherapy remain unsolved issues, as well as the indication of the technique for some subgroups of in situ lesions. Finally, one of the most attractive open forums for debate will be discussed: whether or not completion of axillary dissection in the case of positive SLN is always required.     

Accuracy of fine-needle aspiration cytology of axillary lymph nodes in breast cancer patients: a study of 115 cases with cytologic-histologic correlation

BACKGROUND: Fine-needle aspiration (FNA) cytology of axillary lymph nodes is a simple, minimally invasive technique that can be used to improve preoperative determination of the status of the axillary lymph nodes in patients with breast cancer, thereby serving as a tool with which to triage patients for sentinel versus full lymph node dissection procedures. The aim of the current study was to determine the sensitivity and specificity of FNA cytology to detect metastatic breast carcinoma in axillary lymph nodes. METHODS: A total of 115 FNAs of axillary lymph nodes of breast cancer patients with histologic follow-up (subsequent sentinel or full lymph node dissection) were included in the current study. The specificity and sensitivity, as well as the positive and negative predictive values, were calculated. RESULTS: The positive and negative predictive values of FNA cytology of axillary lymph nodes for metastatic breast carcinoma were 1.00 and 0.60, respectively. The overall sensitivity of axillary lymph node FNA in all the cases studied was 65% and the specificity was 100%. The sensitivity of FNA was lower in the sentinel lymph node group than in the full lymph node dissection group (16% vs 88%, respectively), which was believed to be attributable to the small size of the metastatic foci in the sentinel lymph node group (median, 0.25 cm). All false-negative FNAs, with the exception of 1 case, were believed to be the result of sampling error. There was no 'true' false-positive FNA case in the current study. CONCLUSIONS: FNA of axillary lymph nodes is a sensitive and very specific method with which to detect metastasis in breast cancer patients. Because of its excellent positive predictive value, full axillary lymph node dissection can be planned safely instead of a sentinel lymph node dissection when a preoperative positive FNA result is rendered. .     

Sentinel lymph node biopsy as the new standard of care in the surgical treatment for breast cancer

During the recent years, based on the results of validation studies, the sentinel lymph node biopsy has replaced routine axillary dissection as the new standard of care in early breast cancer. The technique represents a minimally invasive, highly accurate method for axillary staging, which could spare approximately 65–70% of patients unnecessary axillary dissection and its related morbidity. Several technical and clinical controversies have been raised during the development of this new technique; the authors review the most important issues, some questions have already been answered and others are still under debate. As far as the technical aspects are concerned, mapping techniques, appropriate surgical training, options for pathological examination of sentinel lymph nodes and the issue of nonaxillary sentinel lymph nodes are discussed. An update on clinical controversies demonstrates that factors such as large tumor size, palpable axillary nodes, multifocality and multicentricity, previous breast and axillary surgery, and pregnancy are no longer regarded as absolute contraindications for sentinel lymph node biopsy . Feasibility, accuracy and timing of sentinel lymph node biopsy in patients undergoing neoadjuvant chemotherapy remain unsolved issues, as well as the indication of the technique for some subgroups of in situ lesions. Finally, one of the most attractive open forums for debate will be discussed: whether or not completion of axillary dissection in the case of positive SLN is always required.     

Contralateral uptake and metastases in sentinel lymph node mapping for recurrent breast cancer

BACKGROUND AND OBJECTIVES: Sentinel lymph node mapping as a constitutive component in the staging process for invasive breast cancer continues to gain acceptance. We have identified two patients with recurrent invasive breast cancer in whom contralateral sentinel lymph node uptake and metastases, respectively, were detected. Such findings have not been previously reported in our review of the medical literature between 1966 and October 2004. METHODS: Sentinel lymph node mapping was performed on two patients with recurrent invasive breast cancer at our institution. At the time of their index diagnosis, both had received breast conserving surgery and an axillary lymph node dissection with post-operative radiotherapy (RT). All lymph nodes and margins of resection were without tumor. Both patients remained with no evidence of disease for years until routine serial screening mammography was interpreted as suspicious. Each underwent a stereotactic biopsy of the ipsilateral breast corresponding to the mammographic abnormality. Pathology confirmed invasive ductal carcinoma. Both patients refused the recommended salvage mastectomy. PRINCIPAL RESULTS: During a second attempt at breast conservation, sentinel lymph node mapping--which is typically contraindicated for patients with prior axillary surgery--revealed contralateral axillary uptake for both patients. The respective contralateral sentinel node was excised with pathology revealing no tumor in one case, and a microscopic focus of metastatic carcinoma in the second case. MAJOR CONCLUSION: Some patients may benefit from sentinel lymph node mapping prior to salvage mastectomy. Identifying uptake in a contralateral sentinel lymph node may change the multi-disciplinary management of recurrent invasive breast cancer to include a contralateral axillary dissection, chemotherapy, and/or RT to the contralateral axilla.     

乳腔镜前哨淋巴结活检及腋窝淋巴结清扫的临床研究

目的:探讨乳腺癌在乳腔镜下行前哨淋巴结活检及腋窝淋巴结清扫的可行性。方法:通过亚甲蓝示踪对40例Ⅰ、Ⅱ期乳腺癌行乳腔镜前哨淋巴结活检(ESLNB),然后行乳腔镜腋窝淋巴结清扫(EALND),对获得的全部淋巴结行病理检查HE染色,确定前哨淋巴结(SLN)检出率、假阴性率等。结果:40例乳腺癌患者SLN检出率为97.44%(39/40),准确率为94.87%(37/39),灵敏度为94.74%(18/19),假阴性率5.26%(1/19);每例平均前哨淋巴结活检(SLNB)检出数目1-6枚,腋窝淋巴结清扫(ALND)检出数目10-29枚。结论:应用乳腔镜下前哨淋巴结活检和腋窝淋巴结清扫准确可行,美容效果好,并发症低,可对早期乳腺癌进行准确腋窝淋巴结分期。     

Sentinel lymph node biopsy in breast cancer: what a physician should know, a decade after its introduction in clinical practice

In the era of breast conservation surgery, sentinel lymph node biopsy is increasingly used. Sentinel lymph node biopsy can be performed by using the blue dye technique, lymphoscintigraphy and the combined method. Sentinel lymph node biopsy is a minimally invasive technique which has many advantages over the classical axillary (level I and II) lymph node dissection. However, false negative results - albeit rare in experienced hands - may be a serious limitation. The physician should be familiar with this new technique. This will allow him or her to be more actively involved in the management of breast cancer patients and to understand the available management options for these patients.     

乳腔镜前哨淋巴结活检及腋窝淋巴结清扫的临床研究

目的：探讨乳腺癌在乳腔镜下行前哨淋巴结活检及腋窝淋巴结清扫的可行性。方法：通过亚甲蓝示踪对40例Ⅰ、Ⅱ期乳腺癌行乳腔镜前哨淋巴结活检（ESLNB）,然后行乳腔镜腋窝淋巴结清扫（EALND）,对获得的全部淋巴结行病理检查HE染色,确定前哨淋巴结（SLN）检出率、假阴性率等。结果：40例乳腺癌患者SLN检出率为97.44%（39/40）,准确率为94.87%（37/39）,灵敏度为94.74%（18/19）,假阴性率5.26%（1/19）;每例平均前哨淋巴结活检（SLNB）检出数目1-6枚,腋窝淋巴结清扫（ALND）检出数目10-29枚。结论：应用乳腔镜下前哨淋巴结活检和腋窝淋巴结清扫准确可行,美容效果好,并发症低,可对早期乳腺癌进行准确腋窝淋巴结分期。     

Sentinel node detection in breast carcinoma

AIMS AND BACKGROUND: The standard procedure for the evaluation of axillary nodal involvement in patients with breast cancer is still complete lymph node dissection. However, about 70% of patients are found to be free of metastatic disease while axillary node dissection may cause significant morbidity. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this situation. METHODS AND STUDY DESIGN: In a period of 18 months we studied 201 patients with breast cancer, excluding patients with palpable axillary nodes, tumors > 2.5 cm in diameter, multifocal or multicentric cancer, pregnant patients and patients over 80 years of age. Before surgery 99mTc-labeled colloid and vital blue dye were injected into the breast to identify the SLN. In lymph nodes dissected during surgery the metastatic status was examined by sections at reduced intervals. Only patients with SLNs that were histologically positive for metastases underwent axillary dissection. RESULTS: We localized one or more SLNs in 194 of 201 (96.5%) patients; when both techniques were utilized the success rate was 100%. Histologically, 21% of patient showed SLN metastases (7.8% micrometastases) and 68% of these had metastases also in other axillary nodes. None of the patients with negative SLNs developed metastases during follow-up. CONCLUSIONS: At present there is no definite evidence that negative SLN biopsy is invariably correlated with negative axillary status; however, our study and those of others demonstrate that SLN biopsy is an accurate method of axillary staging.     

早期乳腺癌前哨淋巴结活检的研究进展

选择合适的早期乳腺癌病人进行腋窝前哨淋巴结活检,可以减少由腋窝淋巴结清扫导致的并发症。因为腋窝前哨淋巴结活检的假阴性率低,故对前哨淋巴结阴性的病人可以不做进一步腋窝淋巴结清扫。对前哨淋巴结阳性的病人,标准治疗是进一步腋窝淋巴结清扫。腋窝淋巴结放疗可能在保证疗效的前提下,替代腋窝淋巴结清扫,降低由腋窝淋巴结清扫的并发症。     

乳腺癌术中前哨淋巴结印片细胞学的评估

乳腺癌的手术治疗发生了巨大的变化,前哨淋巴结活检是其中之一。前哨淋巴结活检可准确评估区域淋巴结状态,从而避免在腋淋巴结阴性乳腺癌中行腋淋巴结清扫术,减少手术的并发症。乳腺癌前哨淋巴结术中病理学诊断是目前限制前哨淋巴结发展成为乳腺癌的手术规范的主要原因之一,如果能够进行准确地术中诊断,就可以避免再次手术。本文对乳腺癌前哨淋巴结的术中诊断的两种主要方法印片细胞学与冷冻切片的优缺点进行比较,回顾相关机构进行术中诊断的研究结果,并且对印片对诊断前哨淋巴结中存在的问题以及可能改进的方向进行初步的探讨。     

The evolving role of axillary lymph node dissection in the modern era of breast cancer management

The standard of practice in breast cancer surgery is that all patients with a positive sentinel node mandate an axillary lymph node dissection (ALND). Recently, this dogma has been challenged by a trial from ACOSOG (American College Of Surgeons Oncology Group) (Trial Z0011) which demonstrated that patients (without clinically/radiologically apparent axillary metastases) undergoing breast conserving surgery (i.e lumpectomy followed by whole breast radiotherapy) with positive sentinel nodes failed to derive any significant benefit by having an axillary lymph node dissection (ALND) [2]. The logical progression from this study is to question the validity of performing routine axillary lymph node dissections on all patients with positive sentinel lymph nodes (SLN). In addition to the Z0011 trial, there is emerging data that additional patients exist who fail to derive any benefit from axillary surgery. The aim of this article is to discuss the potential subpopulations of patients that may avoid unnecessary ALND in the modern era of breast cancer management.     

Follow-up of cases with false-negative pathologic sentinel nodes in breast cancer

BACKGROUND: The clinical practice of sentinel lymph node biopsy for breast cancer patients started in 1999 in our hospital, to obviate unnecessary axillary lymph node dissection. The present study examines the pathological false-negative cases on intraoperative sentinel lymph node investigations and evaluates their outcomes. METHODS: The subjects consisted of 183 cases with clinically node-negative breast cancer who had undergone sentinel node biopsy. When the sentinel node was noted to contain malignant cells intraoperatively, a complete axillary lymph node dissection was performed subsequently. The patients with tumor free sentinel nodes underwent no further axillary surgery. The pathological false-negative cases in this series were defined as patients with lymph node involvement which was revealed postoperatively, despite negative intraoperative sentinel node examinations. After these surgeries and/or adjuvant therapies, interval clinical evaluations were performed for all patients. RESULTS: Intraoperative diagnosis of the sentinel node was 96.2% accurate compared with the results of permanent sections. There were six pathological false-negative cases, a false-negative rate of 4.1%, all of which had only micrometastasis. Five cases received systemic adjuvant therapy and have been disease-free, however, one patient who refused further therapy developed infraclavicular lymph node metastasis two years after surgery. CONCLUSIONS: In the management of the patients with postoperatively revealed sentinel node micrometastasis, systemic adjuvant therapies might reduce local relapse without secondary lymph node dissection.     

Lymphatic mapping and sentinel node harvesting in patients with recurrent breast cancer

AIMS: To evaluate the feasibility and consequences of lymphatic mapping and a ("repeat") sentinel lymph node (SLN) procedure in patients with breast cancer relapse after previous breast and axillary surgery. METHODS: Review and presentation of a patient cohort. All SLN procedures included lymphoscintigraphy and blue dye injection technique. RESULTS: Twelve cases are described: two patients after a previous SLN procedure and ten after a previous complete axillary lymph node dissection (ALND). Ten patients (83%) had a successful repeat SLN biopsy. After previous ALND, lymphoscintigraphy revealed drainage towards the internal mammary chain in three patients, and contralateral axillary drainage in four. Based on the information from the "repeat" SLN biopsy further treatment strategy was altered in seven of the 12 patients. CONCLUSION: Lymphatic mapping and (repeat) SLN biopsy is possible and can be informative in patients who present with a relapse of breast cancer after previous surgery for primary breast cancer.     

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.     

乳腺癌前哨淋巴结微转移的检测与临床意义

前哨淋巴结(SLN)活检能够准确评估区域淋巴结状态,为乳腺癌患者提供精确的分期,同时也减轻了淋巴结阴性患者的手术并发症.规范前哨淋巴结病理检测手段,充分利用分子生物学检测方法,有助于准确判断微转移.但前哨淋巴结的微转移在乳腺癌预后判断、治疗决策中的意义尚存争议.