Cox C E, Pendas S, Cox J M, Joseph E, Shons A R, Yeatman T, Ku N N, Lyman G H, Berman C, Haddad F, Reintgen D S
Department of Surgery, University of South Florida College of Medicine at the H. Lee Moffitt Cancer Center, Tampa 33612, USA.
Ann Surg. 1998 May;227(5):645-51; discussion 651-3. doi: 10.1097/00000658-199805000-00005.
To define preliminary guidelines for the use of lymphatic mapping techniques in patients with breast cancer.
Lymphatic mapping techniques have the potential of changing the standard of surgical care of patients with breast cancer.
Four hundred sixty-six consecutive patients with newly diagnosed breast cancer underwent a prospective trial of intraoperative lymphatic mapping using a combination of vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine hematoxylin and eosin (H&E) stains and immunohistochemical stains for cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined cluster of positive-staining cells that could be confirmed histologically on H&E sections.
Fine-needle aspiration (FNA) or stereotactic core biopsy was used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422 patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients who failed lymphatic mappings, a complete axillary dissection was performed, and metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26 patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core biopsy. Of interest, there was only one skip metastasis (defined as a negative SLN with higher nodes in the chain being positive) in a patient with prior excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844 (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive SLNs was found in patients who had invasive tumors of increasing size: 18 of 112 patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs. However, a significantly greater percentage of patients (43 of 131 [32.8%] with tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and 5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a positive SLN (p < 0.001).
This study demonstrates that accurate SLN identification was obtained when all blue and hot lymph nodes were harvested as SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a combination of vital blue dye and radiolabeled sulfur colloid is used. Furthermore, these data demonstrate that patients with ductal carcinoma in situ or small tumors exhibit a low but significant incidence of metastatic disease to the axillary lymph nodes and may benefit most from selective lymphadenectomy, avoiding the unnecessary complications of a complete axillary lymph node dissection.
为乳腺癌患者使用淋巴绘图技术制定初步指南。
淋巴绘图技术有可能改变乳腺癌患者的手术治疗标准。
466例新诊断的乳腺癌患者连续接受了一项前瞻性试验，术中使用活性蓝色染料和过滤后的锝标记硫胶体联合进行淋巴绘图。前哨淋巴结（SLN）被定义为蓝色淋巴结和/或热结节，其与非SLN的体外γ探针比率为10:1。所有SLN均被切成两半，进行连续切片，并用常规苏木精和伊红（H&E）染色及细胞角蛋白免疫组化染色进行检查。细胞角蛋白阳性的SLN被定义为任何具有明确阳性染色细胞簇且可在H&E切片上经组织学确认的SLN。
422例乳腺癌患者中的195例（46.2%）通过细针穿刺抽吸（FNA）或立体定向核心活检进行诊断；422例患者中的227例（53.8%）通过切除活检进行诊断。466例患者中的440例（94.4%）成功识别出SLN。466例患者中有26例（5.6%）术中未能识别出腋窝SLN。在所有淋巴绘图失败的患者中，均进行了完整的腋窝清扫，其中26例患者中有4例（15.4%）记录有转移性疾病。在26例淋巴绘图失败的患者中，227例通过切除活检诊断的患者中有11例（4.8%），195例通过FNA或立体定向核心活检诊断的患者中有15例（7.7%）。有趣的是，在一名先前接受切除活检的患者中仅发现1例跳跃转移（定义为SLN阴性而链中较高位置的淋巴结阳性）。每位患者平均获取1.92个SLN。440例患者中的105例（23.8%）切除的SLN中有20%转移性疾病呈阳性。对844个SLN的描述性信息进行了评估：844个中有339个（40.2%）为热结节，844个中有272个（32.2%）为蓝色结节，844个中有233个（27.6%）既是热结节又是蓝色结节。87例非浸润性（原位导管癌）肿瘤患者中有4例（4.6%）发现至少1个阳性SLN。在肿瘤大小不断增加的浸润性肿瘤患者中发现阳性SLN的发生率更高：肿瘤大小在0.1毫米至1厘米之间的112例患者中有18例（16%）SLN呈阳性。然而，肿瘤大小在1至2厘米之间的患者中阳性SLN的比例显著更高（131例中有43例[32.8%]），肿瘤大小在2至5厘米之间的患者中阳性SLN的比例更高（76例中有31例[40.8%]）。肿瘤大小大于5厘米的患者中阳性SLN的发生率最高；在该组中，12例中有9例（75%）SLN呈阳性（p<0.001）。
本研究表明，当将所有蓝色和热淋巴结作为SLN切除时可获得准确的SLN识别。因此，当联合使用活性蓝色染料和放射性标记硫胶体时，淋巴绘图和SLN活检最为有效。此外，这些数据表明，原位导管癌或小肿瘤患者腋窝淋巴结转移疾病的发生率较低但具有显著意义，可能从选择性淋巴结切除中获益最大，避免了完整腋窝淋巴结清扫的不必要并发症。
