200 Sentinel lymph node biopsies without axillary lymph node dissection -- no axillary recurrences after a 3-year follow-up

The aim of this study is to evaluate the rate of axillary recurrences in sentinel lymph node (SLN)-negative breast cancer patients after sentinel lymph node biopsy (SLNB) alone without further axillary lymph node dissection (ALND). Between May 1999 and February 2002, 333 consecutive patients with primary invasive breast cancer up to 4 cm and clinically negative axillae were entered into this prospective study. Sentinel lymph nodes were identified using the combined method with blue dye (Patent blue V) and technetium 99m-labelled albumin (Nanocoll). Sentinel lymph nodes were examined by frozen sections, standard haematoxylin and eosin staining and immunohistochemistry staining. In SLN-positive patients, ALND was performed. Sentinel lymph node-negative patients had no further ALND. The SLN identification rate was 98.5% (328 out of 333). In all, 128 out of 328 (39.0%) patients had positive SLNs and complete ALND. A total of 200 out of 328 (61.0%) patients were SLN negative and had no further ALND. The mean tumour size of SLN-negative patients was 16.5 mm. The mean number of SLNs removed was 2.1 per patient. There were no local or axillary recurrences at a median follow-up of 36 months. The absence of axillary recurrences after SLNB without ALND in SLN-negative breast cancer patients supports the hypothesis that SLNB is accurate and safe while providing less surgical morbidity than ALND. Short-term results are very promising that SLNB without ALND in SLN-negative patients is an excellent procedure for axillary staging in a cohort of breast cancer patients with small tumours.     

Quantitation of sentinel node metastatic burden and Her-2/neu over-expression accurately predicts residual axillary nodal involvement and extranodal disease in breast cancer

Background data

Recent literature has suggested that completion axillary lymph node dissection (ALND) in breast carcinoma patients with positive SLN may not be necessary. However, a method for determining the risk of non-SLN or extranodal disease remains to be established.

Aims

To determine if pathological variables from primary tumors and sentinel lymph node (SLN) metastases could predict the probability of non-sentinel lymph node (NSLN) metastases and extranodal disease in patients with breast carcinoma and SLN metastases.

Methods

84 women with T1-3 breast cancer and clinically-negative axillae underwent completion ALND. Maximum diameter and width of SLN metastases were measured to calculate metastatic area. When multiple SLNs contained metastases, areas were summed to calculate the Total Metastatic Area (TMA). Multiple linear regression models were used to identify predictive factors.

Results

Her-2/neu over-expression increased the odds of NSLN metastases (OR 4.3, p = 0.01) and extranodal disease (OR 7.9, p < 0.001). Independent SLN predictors were ≥1 positive SLN (OR, 7.35), maximum diameter and area of SLN metastases (OR 2.26, 1.85 respectively) and TMA (OR, 2.12). Maximum metastatic diameter/SLN diameter (OR 3.71, p = 0.04) and the area of metastases/SLN area (OR 3.4, p = 0.04) were predictive. For every 1 mm increase in diameter of SLN metastases, the odds of NSLN extranodal disease increased by 8.5% (p = 0.02). TMA >0.40 cm² was an independent predictor for NSLN metastases and extranodal disease.

Conclusion

Her-2/neu over-expression and parameters assessing metastatic burden in the SLN, particularly TMA, predicted the presence of NSLN involvement and extranodal disease in patients with breast carcinoma and SLN metastases.     

乳腺癌前哨淋巴结引流区域的临床研究

目的通过乳腺癌前哨淋巴结（sentinel lymph node,SLN）引流区域的临床研究验证乳腺癌SLN不仅仅是引流乳腺原发肿瘤区域的SLN,而可能是引流整个乳腺器官的SLN。方法选取2004年4月至2008年12月收治的有前哨淋巴结活检（sentinel lymph node biopsy,SLNB）指征而不同意行SLNB替代腋清扫术的103例乳腺癌患者进入该研究。所有患者均以^99m Tc-硫胶体（^99m Tc—SC）注射于乳腺肿瘤表面皮下,染料示踪剂分别注射于乳晕区皮下（73例）或肿瘤对角线部位皮下（30例）。SLNB后施行腋清扫术。结果核素染料联合法、核素法与染料法SLNB成功率分别为100％、97．1％和95．1％（P=0．286）,SLNB的假阴性率分别为7．9％、8．1％和8．1％（P=0．999）。同时获得染料与核素法SLN定位的95例患者,至少有1个SLN被2种方法同时定位,不同部位注射不同示踪剂SLN定位的符合率为100％,有显著相关性（Spearman相关系数0．695,P〈0．01）。结论肿瘤表面、乳晕区、对侧象限的不同部位皮下注射不同的示踪剂可以引流到同一SLN;支持乳腺癌SLN不仅是乳腺肿瘤的SLN,而且是整个乳腺器官的SLN;乳腺癌SLN的新理念有助于临床实践中示踪剂注射部位的个体化和SLNB适应证的扩大。     

Characteristics of Breast Carcinoma Cases With False-Negative Sentinel Lymph Nodes

BackgroundIn the past decade, sentinel lymph node biopsy (SLNB) has become standard for patients with early-stage clinically node-negative breast carcinoma (BC). Despite high overall surgical identification success rates with introduction of the dual-tracer techniques (dye and radiolabeled probe), false-negative rates remained unchanged in most recent meta-analyses.Patients and MethodsWe analyzed cases with false-negative SLN biopsy results over a 12-year period in a single institution to evaluate their clinicopathologic characteristics. Sixty-three false-negative cases (3.1%) were found in 2043 successful SLN mapping procedures, all of which were followed by varying amounts of additional axillary sampling.ResultsThere was a higher proportion of invasive lobular carcinomas (ILCs; 23 cases [37%]) when compared with this lesion's overall reported frequency (5%-15%). The majority of invasive ductal carcinoma (IDC) cases (31 of 40) were poorly differentiated. In 80% of the ductal-type cases, 1 or more nonsentinel nodes (NSLNs) were completely or partially replaced by tumor, as opposed to less than half of such cases of the lobular type. Twenty-two cases had multiple positive NSLN metastases, which were significantly associated with larger tumor size (≥ 1.0 cm) and tumor replacement of NSLNs. Eighty-two percent of the cases with known hormone receptor status were positive for estrogen or progesterone receptors, or both.ConclusionFalse-negative SLN biopsy results were more often associated with a primary BC characterized by a lobular or poorly differentiated ductal histologic type or partial to complete replacement of NSLNs with tumor, or both.     

Sentinel lymph node biopsy to direct treatment in gastric cancer. A systematic review of the literature

Gastric cancer is one of the main causes of cancer-related deaths around the world. The prevalence of early gastric cancer (EGC) among all gastric cancers of 45-51% in Japan, but only 7-28% in Western countries. The prevalence of EGC is growing partly because of better diagnostics and screening programmes. Possible treatment options for EGC treatment are expanded by the introduction of endoscopic mucosal resection and endoscopic submucosal dissection Therefore, detailed knowledge about nodal metastatic risk is warranted. We performed a systematic review of the literature concerning studies investigating the role of sentinel lymph node biopsy in EGCr and whether there is enough proof to introduce SLN as a part of treatment for EGC in the Netherlands. Several detection substances (dye or radiocolloid) and injection methods (submucosal or subserosal) are investigated. An overall sensitivity percentage of 85.4% was found. In comparison, high and clinically sufficient percentages were observed for specificity (98.2%), negative predictive value (90.7%) and accuracy (94%). Subgroup analyses showed that the combination of dye and radiocolloid detection substances is the best method for sentinel lymph node detection in early gastric cancer. However, the precise method of sentinel lymph node biopsy in EGC has to be determined further. Large, randomized series should be initiated in Europe to address this issue.     

A feasibility study (ICG-10) of indocyanine green (ICG) fluorescence mapping for sentinel lymph node detection in early breast cancer

Background

There is now increasing evidence to support the use of indocyanine green (ICG) for sentinel lymph node (SLN) detection in early breast cancer. The primary objective of this feasibility study (ICG-10) was to determine the sensitivity and safety of ICG fluorescence imaging in sentinel lymph node identification when combined with blue dye and radiocolloid.

Methods

One hundred women with clinically node negative breast cancer (95 unilateral; 5 bilateral) had sentinel lymph node (SLN) biopsy using blue dye, radioisotope and ICG. One patient was excluded from analysis and sensitivity, or detection rate, of ICG alone, and in combination with blue dye and/or radioisotope, was calculated for the remaining 104 procedures in 99 patients.

Results

Transcutaneous fluorescent lymphography was visible in all 104 procedures. All 202 true SLNs, defined as blue and/or radioactive, were also fluorescent with ICG. Detection rates were: ICG alone 100%, ICG & blue dye 95.0%, ICG & radioisotope 77.2%, ICG & blue dye & radioisotope 73.1%. Metastases were found in 25 of 201 SLNs (12.4%) and all positive nodes were fluorescent, blue and radioactive. The procedural node positivity rate was 17.3%.

Conclusion

The results of this study confirm the high sensitivity of ICG fluorescence for SLN detection in early breast cancer. The combination of ICG and blue dye had the highest nodal sensitivity at 95.0% defining a dual approach to SLN biopsy that avoids the need for radioisotope.     

Sentinel lymph node biopsy in gastric cancer: Possible applications and limits

Aims

To explore the feasibility and accuracy of sentinel lymph node (SLN) biopsy in gastric cancer.

Patients and Methods

Twenty-nine patients with clinical T1 and T2 N0 M0 gastric cancer less than 5 cm in diameter underwent SLN biopsy with the intraoperative Patent blue method. The procedure continued with radical gastrectomy and D2 lymphadenectomy. We investigated all technical aspects of the blue dye technique and determined the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the SLN technique.

Results

SLNs were detected in 28 of 29 patients; the total number of excised SLNs was 45, with a median of two (range 1-3). Seventeen patients had metastatic SLN, with 21 lymph nodes retrieved. Twenty-two patients had SLNs located at the first level. Four patients had SLNs at the second level, one at the first and second levels, and one at the first and third levels. Five patients had false negative SLNs. The ability of SLN biopsy to predict the status of the other lymph nodes was summarised by an accuracy of 75%, a sensitivity of 75%, a specificity of 75%, a positive predictive value of 88%, and a negative predictive value of 55%.

Conclusions

Our study demonstrates that pick-up SLN biopsy in gastric cancer is technically feasible but has very low sensitivity. Regarding the utility of SLN navigation when attempting to detect the nodal basin, the high rate of false negative SLNs and lymph node level jumping warrant further studies with a large accrual before the method can be introduced into daily practice.     

Current trends of sentinel lymph node biopsy for breast cancer —A surgeon’s perspective

Sentinel lymph node biopsy (SLNB) is standard care for patients with early-stage breast cancer, and axillary lymph node dissection (ALND) is considered unnecessary when sentinel lymph nodes (SLNs) are tumor-free. Additional non-SLN metastasis in patients with positive SLNs can be estimated using several risk factors such as primary tumor size, metastatic tumor size in SLNs, lymphatic vessel invasion, and so on. All patients with positive SLNs may be treated with further ALND based on their own risk for nonSLN metastasis. Recent randomized clinical trials have already proved less surgical morbidity and better QOL for SLNB alone compared with ALND. However, trials concerning the efficacy of ALND in positive SLNB patients in preventing local regional recurrence and improving overall survival compared with no ALND, and also, concerning the effectiveness of ALND compared with axillary radiation therapy (RT), have not yielded clear results. The prognostic significance of micrometastasis in SLNs or bone marrow also remains to be determined. So far SLNB is not acceptable for patients with positive nodes in the axilla at initial diagnosis even if their axillary metastases are down-staged to negative by neoadjuvant chemotherapy. Although basically SLNB does not need to be performed for patients with pure ductal carcinoma in situ (DCIS), it is recommended for patients with an initial diagnosis of DCIS which is large, palpable, high grade, or found in younger patients. Because these types of DCIS have higher incidences of accompanying invasive lesions. In addition if patients will undergo mastectomy, SLNB is recommended because of the inability to perform SLNB after mastectomy. SLNB may be acceptable for patients with T3 or T4b tumors, even though SLN identification is lower yet SLN involvement is higher compared with T1 or T2 tumors, and systemic adjuvant therapy is more important for patients with T3 or T4b tumors. SLNB is a bridge to further axillary treatment such as ALND or axillary RT, and which strategy, including no further treatment, is best considered individually based on recurrence risk, treatment responsiveness and use or non-use of systemic therapy.     

早期乳腺癌腋窝前哨淋巴结活检的研究现状

自从1894年Halsted创立了乳腺癌根治术以来,腋窝淋巴结清扫术(axillary lymph nodes dissection,ALND)一直是乳腺癌外科治疗的重要组成部分,对临床分期、判断预后、指导治疗以及防止局部复发具有非常重要的临床意义。近年来     

乳腺癌淋巴引流途径的临床研究

目的探讨乳腺癌时乳腺淋巴引流的特点。方法以2004年11月至2006年5月期间住院的206例乳腺癌患者为研究对象，其中191例术前行淋巴闪烁显像。用前哨淋巴结活检和腋窝溶脂后腔镜观察联合验证淋巴闪烁显像所见的乳腺淋巴引流途径和前哨淋巴结。结果肿瘤周围腺体实质和肿瘤被覆皮下联合注射示踪剂内乳前哨淋巴结显示率为46．8％。淋巴显像、前哨淋巴结活检和腋窝溶脂后腔镜3种方法联合观察发现乳腺淋巴经不同输入淋巴管直接引流到腋窝或内乳区；腋窝前哨淋巴结位于第2肋骨与胸大肌外缘交界处周围，少数患者有浅、深两组腋窝前哨淋巴结。内乳淋巴结转移率为26．2％，腋窝淋巴结转移≥4枚时内乳转移率为50．7％。第2肋间隙是内乳淋巴结最常见的转移部位。内乳淋巴结转移与肿瘤部位或大小无显著相关性。结论乳腺实质及皮肤的淋巴沿各自的集合淋巴管不经乳晕淋巴丛而直接汇人腋窝或内乳淋巴结；多数患者不同的淋巴管在腋窝汇人同一前哨淋巴结，少数汇人深浅不同组前哨淋巴结。有选择地行内乳淋巴结活检有助于乳腺癌的精确分期、治疗和预后判断。     

Sentinel lymph node biopsy without axillary dissection after an intraoperative negative histological investigation in 358 invasive breast cancer cases

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important treatment option for breast cancer patients, as it can accurately predict axillary status. Our previous study using dye with or without radioisotope showed the accuracy and sensitivity of SLNB to be 97% and 94%, respectively. Based on these results, axillary lymph node dissection (ALND) was eliminated starting in January, 1999 in patients with intraoperatively negative SLNB at our institution. The present study shows the results and outcomes of SLNB as a sole procedure for patients with invasive breast cancer. PATIENTS AND METHODS: Three-hundred-fifty-four patients and 358 cases of invasive breast cancer (4 bilateral breast carcinoma) treated with SLNB alone after an intraoperative negative SLNB were studied prospectively from January 1999 to December 2001. RESULTS: The number of the identified SLNs per case ranged from 1 to 8 (mean, 2.5). Of a total of 358 cases, 297 (83%) were treated with hormone therapy and/or chemotherapy, and 281 (78%) were treated with radiotherapy to the conserved breast (50 Gy+/-10 Gy boost), the axilla (50 Gy), or the both sites. After a median follow-up of 21 (range 6-42) months, no patient developed an axillary relapse. Four cases initially recurred in distant organs and one case in the conserved breast. CONCLUSIONS: Our results indicate that an intraoperative negative SLNB without further ALND may be a safe procedure when strict SLNB is performed. To better assess the safety, however, may require longer follow-up.     

Avoidance of axillary lymph node dissection in selected patients with node-positive breast cancer

Aims

Currently, it is standard practice to avoid ALND in patients with negative SLN, whereas this procedure is mandated for those with positive SLN. However, there has been some debate regarding the necessity of complete ALND in all patients with positive SLN. This review article discusses the issues related to eliminating the need for ALND in selected patients with positive nodes.

Methods

A review of the English language medical literature was performed using the MEDLINE database and cross-referencing major articles on the subject, focusing on the last 10 years.

Results

Currently, complete ALND is mandated in patients with SLN macrometastases as well as those with clinically positive nodes. It is not clear whether SLN biopsy is appropriate for axillary staging in patients with initially clinically positive nodes (N1) that become clinically node-negative (N0) after neoadjuvant chemotherapy. Although there is debate regarding whether ALND should be performed in patients with micrometastases in the SLN, it seems premature to abandon ALND in clinical practice. Moreover, it remains unclear whether it is appropriate to avoid complete ALND in patients with ITC-positive SLN alone.

Conclusions

In the absence of data from randomised trials, the long-term impact of SLN biopsy alone on axillary recurrence and survival rate in patients with SLN micrometastases as well as those with ITC-positive SLN remains uncertain. These important issues must be determined by careful analysis of the results of ongoing clinical trials.     

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.     

Sentinel node biopsy to avoid axillary lymph node dissection in breast cancer

The role of sentinel node biopsy in breast cancer has increased over the last few years. Sentinel nodes can predict the status of all axillary lymph nodes precisely and select patients with negative nodes for whom axillary dissection is unnecessary. Many problems remain, such as the ideal injection technique, ideal agents, and ideal histological detection of sentinel node metastases, and must be addressed before sentinel node biopsy becomes the standard of care for patients with breast cancer.     

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。     

Sentinel node biopsy in breast cancer

Axillary lymphnode dissection (ALND) for breast cancer patients provides local control and information for the determination of the type of adjuvant therapy. The benefit of axillary surgery itself for survival is considered to be limited to patients with positive nodes. Sentinel node biopsy is a recently developed, minimally invasive technique for precisely predicting axillary nodal status. As this technique has less morbidity and greater accuracy than ALND, it replaces ALND for patients with node negative breast cancer. In this report, we outline the current status of sentinel node biopsy for breast cancer patients and introduce our preliminary results.     

Dye- and gamma probe-guided sentinel lymph node biopsy in breast cancer patients: using patent blue dye and technetium-99m-labeled human serum albumin

BACKGROUND: Sentinel lymph node (SLN) biopsy is a promising method for the diagnosis of the axillary nodal status. We examined the availability of the SLN biopsy using two mapping procedures: the dye- and gamma probe-guided method, and preoperative lymphoscintigraphy by gamma camera imaging. METHODS: We enrolled 48 patients with breast cancer. Technetium-99m-labeled human serum albumin was injected into the subdermal tissue above the primary tumor or biopsy cavity, and preoperative gamma camera imaging was performed. After induction of general anesthesia, patent blue dye was injected into the peritumoral area prior to the surgical procedure. A handheld gamma-detection probe was used to assist in SLN detection. Careful dissection was performed to identify blue-stained afferent lymphatic vessels and nodes. An SLN was defined as any blue and/or radioactive node, and was excised. After SLN biopsy, axillary lymph node dissection of level I, II, and III was completed, in order to confirm the diagnostic ability of the SLN biopsy. RESULTS: Intraoperative SLN identification of axillary lesions was successful in 43 of 48 patients (90%). The dye- and gamma probe-guided method was successful in 25 patients (52%), the dye-guided method alone succeeded in 11 patients (23%), and the gamma probe-guided method alone succeeded in 7 patients (15%). Preoperative lymphoscintigraphy revealed axillary focal accumulations in 29 of 48 patients (60%). All patients who underwent successful preoperative SLN identification by lymphoscintigraphy had successful intraoperative SLN identification. A diagnostic accuracy of 95%, a sensitivity of 89%, and a specificity of 100% were achieved in the diagnosis of axillary metastasis. Internal mammary SLNs were identified in four patients intraoperatively, but we could not detect cancer metastasis in the internal mammary SLNs. CONCLUSIONS: The dye-guided and gamma probe-guided methods were complementary. Preoperative lymphoscintigraphy was useful to predict intraoperative SLN identification. Further study is necessary to assess the role of SLN biopsy of the internal mammary lymph nodes.     

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.     

前哨淋巴结时代乳腺癌的精准区域处理：演进与展望

区域淋巴结状况是乳腺癌重要的预后指标之一,可以指导分期和辅助治疗策略的制定。近30年来乳腺癌前哨淋巴结活检术（sentinel lymph node biopsy,SLNB）研究发展迅速,循证医学Ⅰ类证据支持其为临床腋窝淋巴结阴性早期乳腺癌患者安全、有效的腋窝分期技术,前哨淋巴结阴性及低肿瘤负荷患者SLNB替代腋窝淋巴结清扫术后腋窝复发风险和并发症极低。乳腺癌局部区域控制新理念——应该综合考虑远处转移风险、全身治疗效果与不良反应以及局部区域治疗（手术/放疗）效果与不良反应——推动了SLNB适应人群不断扩展,新辅助治疗与SLNB、内乳SLNB将进一步促进区域淋巴结处理降阶梯,豁免腋窝手术临床研究值得期待。SLNB标志着乳腺癌区域淋巴结迈入微创化精准诊疗时代。本文就前哨淋巴结时代乳腺癌的精准区域处理的演进过程和最新进展进行总结,以期为广大临床工作者提供参考。