乳腺癌患者的局麻下前哨淋巴结活检

1 引 言 乳腺癌治疗概念已经从最大可耐受治疗转变为最小有效治疗.从腋窝淋巴结切除(ALND)转变为前哨淋巴结活检(SLNB).如果远处转移的癌细胞已经播散到腋窝淋巴结则乳腺癌播散到腋窝淋巴结这一主流理论被确定.接受来自肿瘤的淋巴管引流的第一个淋巴结称为前哨淋巴结.我们可以发现前哨淋巴结并且检测它是否存在癌细胞.如果前哨淋巴结没有癌症,那就没必要切除其余剩下的腋窝淋巴结.这种找到前哨淋巴结的方法就是注射异硫蓝染料或放射同位素进入乳腺区域然后仔细解剖找到第一个淋巴结并将前哨淋巴结移送病理学家通过冷冻切片来鉴定.如果这没有远处转移的癌细胞存在于淋巴结中,外科医师可以不用处理腋窝淋巴结(ALND).     

淋巴闪烁显像与乳腺癌前哨淋巴结活检

乳腺癌前哨淋巴结的精确定位是乳腺癌前哨淋巴结活检成功的先决条件之一,明确乳腺淋巴引流途径对乳腺癌前哨淋巴结的准确定位有重要指导意义。术前淋巴闪烁显像可提供个体化的淋巴引流特点,有助于确定前哨淋巴结的位置、数目及是否存在腋窝外前哨淋巴结。现对淋巴闪烁显像在乳腺癌前哨淋巴结活检中的应用现状和存在的问题进行综述。     

乳腺癌前哨淋巴结活检存在的几个问题

前哨淋巴结活检（SLNB）在乳腺外科已被广泛应用，但仍有一些问题存在争议，如示踪剂的选择、示踪剂注射的最佳部位、如何评价淋巴闪烁显像、腋窝外前哨淋巴结（SLN）特别是内乳SLN的意义、SLN微转移的检测及其意义、SLNB对导管原位癌患者的意义、新辅助化疗对SLNB的影响以及腋窝淋巴结清扫的价值等问题。笔者对乳腺癌SLNB的现状和当前存在的问题进行综述，希望有助于规范该技术并促进其病例选择的一致性。     

Pre-operative lymphoscintigraphy before sentinel lymph node biopsy for breast cancer

Pre-operative lymphoscintigram for axillary sentinel lymph node biopsy (SLNB) may not be required for successful SLNB. The 117 consecutive patients who underwent SLNB had pre-operative lymphoscintigraphy. The operating surgeon was blinded to the results of the lymphoscintigram before SLNB. After SLNB was complete, the surgeon was unblinded to the results of the lymphoscintigram; re-exploration carried out if more nodes were predicted on the lymphoscintigram. 116 patients (99%) had successful SLNB before unblinding. In 85 patients (73%), operative findings corresponded with scintigraphic findings. In 26 patients (22%), the lymphoscintigram predicted more sentinel nodes than had been found; further nodes were identified and excised in only 4 patients (3%). None were positive for cancer. SLNB was successful in 99% of cases without pre-operative lymphoscintigraphy. Only 3% of patients had further nodes identified as a result of the lymphoscintigram. Pre-operative lymphoscintigraphy does not improve the ability to perform axillary SLNB during breast cancer surgery.     

Technical advances in sentinel lymph node biopsy for breast cancer

Technical advances in the past several years have simplified and improved sentinel lymph node (SLN) biopsy for breast cancer. The use of alternative injection sites (skin or subareolar) yields high SLN identification rates and may shorten the learning curve associated with standard peri-tumoral injection. The dual-agent (radiocolloid plus blue dye) technique is now recommended to decrease false-negative rates, especially when surgeons are just learning how to perform SLN biopsy. Methylene blue may be an acceptable substitute for isosulfan blue dye and is associated with fewer hypersensitivity reactions. Hand-held gamma probes are now smaller and more maneuverable, with better shielding for directional detection of gamma rays. Routine preoperative lymphoscintigraphy can be avoided, thus facilitating operating room scheduling. Surgeons can use minimally invasive techniques to identify and remove internal mammary SLNs.     

Current controversies in sentinel lymph node biopsy for breast cancer

Despite the widespread use of sentinel lymph node biopsy (SLNBx) in the surgical management of breast cancer patients, several areas remain controversial. The following controversies are reviewed: Learning curves and validation studies. There clearly is a learning curve, and a completion ALND should be done until adequate proficiency is exhibited, both in terms of identification and false-negative rates. Location of injection. Intradermal injection offers superior identification rates compared with peritumoral injection, with comparable false-negative rates. Subareolar injection is as accurate as peritumoral injection. The value of scintigraphy. Routine scintigraphy does not enhance identification or false-negative rates. Mapping agents. Blue dye and radioactive tracer combined to provide a higher identification rate than either used alone.SLNBx in DCIS. In patients with a high risk of microinvasion, such as large tumors, a mass or high-grade DCIS-SLNBx is justified.SLNBx following neoadjuvant chemotherapy. Although there is evidence that SLNBx after neoadjuvant chemotherapy may be accurate, these data should be applied cautiously. Implications of non axillary SLN, especially internal mammary nodes. Data do not support routine resection of internal mammary sentinel lymph nodes outside a clinical trial.Implications of micrometastases in the sentinel lymph node seen only on immunohistochemistry. Since the significance of such metastases is unclear, decisions regarding treatment of these patients should be individualized. The value of completion axillary lymph node dissection. Is being addressed in clinical trials. Until those studies mature, completion ALND should be performed for patients with SLN metastases, but may be abandoned for patients with a negative SLN.     

Axillary recurrence after sentinel lymph node biopsy for breast cancer

Sentinel lymph node biopsy (SLNB) is routinely performed as an axillary staging procedure for breast cancer. Although the reported false-negative rate approaches 10 per cent, this does not always lead to axillary recurrence. We previously reported an axillary recurrence rate of 1 per cent at a median follow-up of 2 years. Our objective is to determine the rate of axillary recurrence with longer follow-up. A retrospective review of patients with invasive breast cancer and a negative SLNB treated between 2001 and 2005 was performed. Cases where neoadjuvant therapy was used or where isolated tumor cells (ITCs) were found were included, whereas those with fewer than 18 months of follow-up were excluded. One (0.7%) out of 139 patients had an axillary recurrence after a median follow-up of 52 months. No patient who underwent neoadjuvant chemotherapy or with ITCs had axillary recurrence. Twelve (8.6%) patients have died, with death attributed to breast cancer in three. Our study demonstrates that axillary recurrence after SLNB remains a rare event after a median follow-up of 52 months, despite including potentially higher risk scenarios such as where neoadjuvant chemotherapy is used and ITCs are found. Therefore, axillary lymph node dissection can safely be avoided in patients where SLNB is negative.     

乳腺癌前哨淋巴结活检的实践与体会

目的评价乳腺癌前哨淋巴结活检(sentinel lymph node biopsy,SLNB)的可行性,并分析影响该技术成功率的相关因素。方法术前于肿瘤周围皮内分别注射放射性胶体和蓝色染料两种前哨淋巴结示踪剂,术前先行淋巴闪烁扫描,术中应用γ计数探测仪检测,并结合淋巴结蓝染情况定位SLN,切除SLN后再行腋窝淋巴结清扫(axillary lymph node dissection,ALND),两标本均行组织学检查。结果全组116例乳腺癌SLNB的检出率98.3%,该技术的灵敏度93.6%,准确性97.4%,假阴性6.4%。结论乳腺癌SLNB是一种简便、安全的检测技术,可用于了解腋窝淋巴结的状况,有望在早期乳腺癌中取代常规的ALND。     

Mastectomy and concomitant sentinel lymph node biopsy for invasive breast cancer

BACKGROUND: Although sentinel lymph node biopsy (SNLB) has become a standard ancillary to breast conservation, there remains a hesitancy to perform SLNB concomitant with mastectomy primarily because of concerns regarding reoperation for a positive SLN. METHODS: A retrospective review of 51 patients who underwent SLN biopsy concomitantly with mastectomy for invasive breast cancer was performed. In addition, a survey was sent to surgical oncologists who routinely perform SLNB in conjunction with mastectomy. RESULTS: The SLN was identified in 98% of patients, and an average of 2.4 SLNs/patient were removed. The SLN was positive in 14 patients (27%). Ten patients underwent axillary lymph node dissection as a second procedure; an average of 15.4 +/- 6 nodes were cleared, and there were no complications. Although techniques vary greatly among surgeons, the majority believe that a subsequent ALND procedure does not carry additional risk of morbidity. CONCLUSIONS: Mastectomy and concomitant SLNB is a safe option for well-selected breast cancer patients. Results appear acceptable using a variety of techniques. Patients with a positive SLN can safely undergo completion axillary lymph node dissections. This includes patients who have undergone immediate reconstruction, but proper planning is needed to minimize potential risks.     

Current European studies of sentinel lymph node biopsy for breast cancer

The paradigm shift in the assessment of the axilla in breast surgery has evoked specific clinical issues. In a population where breast cancer is diagnosed early and service screening mammography is applied, the chance for a woman to be free of lymph node metastases is approximately 60%. Currently, there are three ongoing and one published randomized series on sentinel node lymphadenectomy in Europe, comprising more than 100 patients. These studies address the important issues of morbidity, quality of life and long-term outcome measures such as survival and recurrence.     

False-negative frozen section of sentinel lymph node biopsy for breast cancer

A prospective study is presented of frozen section examinations (FS) performed in parallel with 265 consecutive sentinel lymph node procedures (SLNP) over a 20-month period. The final pathological study included immunohistochemistry (IHC) for keratin if the haematoxylin-eosin (HE)-stained section was tumour free. FS correctly identified node-positive or node-negative axillae in 235 cases. In 28 SLNPs the final examination gave a positive result not detected in the FS, resulting in reoperation. In 21 of these false-negative (FN) cases micrometastases (MIM) were present. There were no false-positive cases, but in two cases of lobular carcinoma the findings in the FS were equivocal, the final reports recording metastases in one but not in the other. Lobular carcinoma and other less common subtypes of carcinoma were overrepresented, ductal carcinoma not otherwise specified (NOS) being less likely to affect the FN findings.     

乳腺癌前哨淋巴结活检临床意义研究

目的 评价前哨淋巴结活检术（SLNB）预测腋窝淋巴结（ALN）转移状况的准确性及临床意义。方法 2002年6月至2005年6月对120例女性乳腺癌病人联合使用关蓝溶液及^99mTc-右旋糖酐（DX）示踪，γ记数探测仪定位，行SLNB。结果 前哨淋巴结（SLN）检出率为98．3％，准确率为97．5％，假阴性率为6．5％，冰冻切片和连续石蜡切片加免疫组化检查的符合率为92．4％。结论 SLNB可以准确预测ALN转移状况；联合法并术中使用γ记数探测仪是SLN定位的首选方法；多枚ALN转移可能使假阴性率升高。     

Subareolar injection for sentinel lymph node biopsy in multiple breast cancer

In this study we performed subdermal injection of 99mTc-labeled albumin combined with subareolar (SA) injection of blue dye to axillary lymphatic mapping and sentinel lymph node biopsy (SNLB) in patients with multifocal and multicentric breast cancer (MC) to evaluate the feasibility and accuracy of this technique. We compared the results with a group of patients with unifocal breast cancer. From January 1999 to March 2006 axillary lymph node mapping and SLNB was performed on 250 patients followed by a complete axillary lymph node dissection. Retrospective analysis showed that 32 (12.8%) of these patients have MC on final histopathologic examination and 218 (87.2%) have unifocal cancer. In statistical analysis tumor size shows a significant difference (p=.01) with largest lesions in MC. In MC often histological type is invasive lobular with or without in situ cancer (p= .001). Metastatic lymph node involvement was significantly higher in the MC group compared to unifocal cancer group (p=.001). False negative (FN) rate was 5.8% in MC and 9.6% in unifocal cancers. The overall accuracy of lymphatic mapping was 96.8% in MC and 97.6% in unifocal cancers. Sensitivity was 94.4% in MC and 91.2% in unifocal cancers. In this study we provide further evidence that lymphatic mapping may be reliable even in patients with MC. SA injection technique demonstrates a high sentinel lymph node identification rate and low FN rate; therefore this technique should been recommended to SLNB in patients with MC of the breast.     

乳腺癌前哨淋巴结活检的研究进展

乳腺癌前哨淋巴结（SLN）活检被认为是决定是否行腋窝淋巴结清扫术的潜在手段。多年研究表明，SLN活检能较准确地评估早期乳腺癌患者的腋窝淋巴结情况，其近期疗效与腋窝淋巴结清扫术相当。笔者主要对近年乳腺癌SLN活检的研究进展作一综述。     

Axillary regional recurrence after sentinel lymph node biopsy for breast cancer

The accuracy of sentinel lymph node biopsy (SLNB) staging in breast cancer has been demonstrated in studies comparing it with axillary dissection. There is a 5 per cent false-negative rate, but this does not always correlate with axillary recurrence. Our purpose was to determine the rate of axillary lymphatic recurrence in breast cancer patients who had a negative SLNB. We conducted a cohort study of breast cancer patients who underwent SLNB between 2001 and 2005. Only patients who had a negative SLNB were included. Patient demographics and tumor factors were reviewed. Outcomes measured were axillary and systemic recurrence and survival. Eighty-nine patients with a mean age of 54.4 +/- 9.9 years were included. Eighty-nine per cent of cases had infiltrating ductal carcinoma histology. Mean tumor size was 19 +/- 14 mm. Breast conservation surgery was done in 65 cases and mastectomy in 24. A mean of 2.3 +/- 2.4 SLN were found. After a median follow-up of 2.15 years, 1 (1%) patient developed a lymphatic recurrence in the axilla. SLNB provides accurate staging of breast cancer. Patients with negative SLNB do not require axillary dissection.     

Meta-analysis of sentinel lymph node biopsy in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive way to diagnose axillary lymph node (ALN) metastases in breast cancer. The most important features are ability to identify the SLN (I.D. rate), how often the SLN and ALN pathology match (concordance), and how often the SLN is negative for cancer when the ALNs are positive (false negative). Technique and patient criteria for SLNB vary among studies. This study performed meta-analysis of published studies to determine the I.D., concordance, and false negative rate (1) overall and for (2) both blue dye and radiocolloid, (3) the injection method, (3) palpable and nonpalpable ALNs, and (4) invasive and in situ disease. METHODS: Inclusion criteria were patients with breast cancer who had SLNB followed by ALN dissection with H&E staining. Meta-analysis was performed using analysis of variance with each observation weighted inversely to its variance. P < 0.05 was considered significant. RESULTS: Eleven studies (n = 912) met the inclusion criteria. Overall, 762 (84%) SLNs were identified, concordance was 747/762 (98%), and 15/296 (5%) were falsely negative. Highest I.D. rates (P < 0.05) were reported with albumin radiocolloid or dye + radiocolloid (97 and 94%, respectively), with injection around an intact tumor (96%), with invasive cancer (95%), and in the clinically negative axilla (96%). Concordance and false negative rates did not vary. CONCLUSIONS: The SLN can be identified in over 97% of patients if certain techniques and inclusion criteria are used. SLNB reflects the status of the axilla in 97% of cases and has a 5% false negative rate.