乳腺癌前哨淋巴结活检技术的临床应用

目的:探讨前哨淋巴结活检(Sentinel lymph node biopsy,SLNB)在乳腺癌外科中的应用,并评价其准确性及可行性.方法:对2002-01～2004-01我院收治的161例Ⅰ、Ⅱ期乳腺癌病例,在常规行乳腺癌手术前均进行SLNB,即肿瘤局部皮内联合注射99mTc-DX及美蓝,根据核素示踪及美蓝染色结果寻找SLN并摘除,行冰冻病理检查.将SLNB结果与术后腋窝淋巴结病理结果进行分析.结果:161例中149例发现SLN,检出率为92.5%(149/161);共检出SLN273个,平均1.83个/例.比较SLNB与术后病理结果,SLNB检出灵敏度为96.1%(49/51),准确性98.7%(147/149),假阴性率3.9%(2/51),假阳性率0。结论:SLN可比较准确地反映腋窝淋巴结状况,SLNB是乳腺癌治疗中的实用技术.     

Radioguided sentinel lymph node biopsy in breast cancer surgery.

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way through the lymphatic system, from the first to upper levels. Therefore, the first lymph node met (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes are affected. Because axillary node dissection does not improve prognosis of patients with breast cancer (being important only to stage the axilla), sentinel lymph node biopsy might replace complete axillary dissection to stage the axilla in clinically N0 patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that, after surgery, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Furthermore, histologic sampling errors can be reduced if a single (sentinel) node is assessed extensively rather than few histologic sections in a high number of lymph nodes per patient. Although the pattern of lymph drainage from breast cancer can be variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Therefore, considering that tumor lymphatics are disorganized and relatively ineffective, subdermal and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100- to 200-nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the axilla must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when needed, immune staining with anticytokeratin antibody. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94%--97% in institutions where a high number of procedures are performed and approaches 99% when combined with the vital blue dye technique. At present, there is no definite evidence that negative sentinel lymph node biopsy is invariably correlated with negative axillary status, except perhaps for T1a-b breast cancers, with a size of < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection on patients with a negative sentinel lymph node on the long-term clinical outcome of patients.     

吲哚菁绿在乳腺癌前哨淋巴结活检中的应用观察

目的 探讨吲哚菁绿(ICG)单独应用于乳腺癌前哨淋巴结(SLN)活检的临床应用前景.方法 选择2014年7-12月接受手术的72例女性乳腺癌患者,年龄33～67岁,中位年龄50岁,随机分为实验组(n=35)和对照组(n=37),分别以ICG和亚甲蓝作为示踪剂实施SLN活检.手术切除标本送快速冰冻病理检测,证实存在SLN转移者,行腋窝淋巴结清扫,SLN阴性者不行腋窝淋巴结清扫.结果 ICG法检出率为94.3％,成功检出SLN 111个,平均每例检出3.2个SLN,准确率94.3％,灵敏度100％,假阴性率0％;亚甲蓝法检出率为91.9％,成功检出SLN 78个,平均每例检出2.1个SLN,准确率89.2％,灵敏度92.9％,假阴性率为7.7％.两组平均检出个数和假阴性率差异有统计学意义(P＜0.05),检出率、准确率、灵敏度差异无统计学意义(P＞0.05).结论 采用ICG法进行SLN活检成功率高,假阴性率低,临床效果优于亚甲蓝法,有望单独应用于乳腺癌SLN活检.     

Pre-operative sentinel lymph node localization in breast cancer with superparamagnetic iron oxide MRI: the SentiMAG Multicentre Trial imaging subprotocol

Objective:

Sentinel lymph node biopsy (SLNB) with a superparamagnetic iron oxide (SPIO) tracer was shown to be non-inferior to the standard combined technique in the SentiMAG Multicentre Trial. The MRI subprotocol of this trial aimed to develop a magnetic alternative for pre-operative lymphoscintigraphy (LS). We evaluated the feasibility of using MRI following the administration of magnetic tracer for pre-operative localization of sentinel lymph nodes (SLNs) and its potential for non-invasive identification of lymph node (LN) metastases.

Methods:

Patients with breast cancer scheduled to undergo SLNB were recruited for pre-operative LS, single photon emission CT (SPECT)-CT and SPIO MRI. T₁ weighted turbo spin echo and T₂ weighted gradient echo sequences were used before and after interstitial injection of magnetic tracer into the breast. SLNs on MRI were defined as LNs with signal drop and direct lymphatic drainage from the injection site. LNs showing inhomogeneous SPIO uptake were classified as metastatic. During surgery, a handheld magnetometer was used for SLNB. Blue or radioactive nodes were also excised. The number of SLNs and MR assessment of metastatic involvement were compared with surgical and histological outcomes.

Results:

11 patients were recruited. SPIO MRI successfully identified SLNs in 10 of 11 patients vs 11 of 11 patients with LS/SPECT-CT. One patient had metastatic involvement of four LNs, and this was identified in one node on pre-operative MRI.

Conclusion:

SPIO MRI is a feasible technique for pre-operative localization of SLNs and, in combination with intraoperative use of a handheld magnetometer, provides an entirely radioisotope-free technique for SLNB. Further research is needed for the evaluation of MRI characterization of LN involvement using subcutaneous injection of magnetic tracer.

Advances in knowledge:

This study is the first to demonstrate that an interstitially administered magnetic tracer can be used both for pre-operative imaging and intraoperative SLNB, with equal performance to imaging and localization with radioisotopes.     

乳腺癌保乳手术联合哨兵淋巴结活检术临床疗效观察

目的观察乳腺癌保乳手术及哨兵淋巴结活检的临床疗效。方法 62例临床确诊的早期乳腺癌患者,均行区段切除及哨兵淋巴结活检手术,其中10例哨兵淋巴结阳性者加腋淋巴结清扫术,术后行根治性放疗,并根据临床评价38例行辅助化疗,36例内分泌治疗。结果术后随访24～106个月,中位随访53个月,1例3年内复发,2例5年内复发,局部复发率4.8%。复发者均改行乳腺癌改良根治术。结论对于临床早期乳腺癌患者,保留乳房及哨兵淋巴结活检术可行,术后辅以放疗、化疗及内分泌治疗能够获得满意效果。     

Non-visualization of sentinel lymph node in patients with breast cancer

Histological evaluation of the first draining lymph node (sentinel node) in the axilla of patients with breast cancer has dramatically altered the surgical approach to these patients, with sparing of the axilla if no tumour cells are identified. In a fraction of patients imaged after peri-tumoural injection of the breast, there is no visualization of the sentinel node. We retrospectively analysed the status of patients whose nodes were visualized and of patients whose nodes failed to visualize, to define the variables associated with non-visualization of the sentinel node. Seventy-four breast cancer patients were imaged following peri-tumoural injection of filtered 99Tc(m)-sulfur colloid, immediately and up to 5.5 h post-injection. The scintigraphic data were analysed with reference to the patient's age, histology, grade, site and size of tumour, previous diagnostic procedure and time interval to scan, using univariate analysis and a logistic regression model. A sentinel node was visualized in 53 of 74 women (72%). Comparison of patients with non-visualized versus visualized sentinel nodes disclosed no statistically significant univariate relation to age of the patients (P = 0.10), size of tumour (P = 0.46), site (P = 0.26), histology [invasive ductal carcinoma in 16 of 20 (80%) non-visualized cases, and in 43 of 53 (81%) visualized patients], prior excision biopsy (P = 0.36) and time interval to surgery (P = 0.29). Tumour grade was the only significant variable on univariate analysis (P = 0.03), though multivariate analysis showed that none of the independent parameters were statistically significant. In 39 patients with an upper outer quadrant tumour, the location of the sentinel node was not limited to the axilla and even crossed the midline of the breast. Our results show that none of the independent variables is associated with non-visualization of sentinel lymph node on preoperative lymphoscintigraphy of patients with breast cancer, though the tumour grade may have contributed to non-visualization of this node. The non-axillary drainage from upper outer quadrant tumours suggests the routine use of lymphoscintigraphy prior to axillary dissection.     

应用γ探测仪探测乳腺癌前哨淋巴结的临床价值

目的 探讨应用γ探测仪探测乳腺癌前哨淋巴结活组织检查（SLNB）的临床价值。方法 53例乳腺癌患者，在肿块或活组织检查腔周围的乳腺实质内注射^99Tc^m－硫胶体，应用γ探测仪术中定位切除放射性浓聚的前哨淋巴结（SLN），再行腋窝淋巴结清扫（ALND）。SLN与腋窝淋巴结（ALN）同时行HE和免疫组织化学（IHC）检测，以及用逆转录多聚酶链反应（RT－PCR）检测CK19 mRNA的表达，观察SLN的检出率和用SLN预测ALN转移的准确性，评价SLN阴性的早期乳腺癌患者用SLNB代替ALND的可行性。结果 SLN检出灵敏度为91％（48／53例），共检出SLN91枚，平均1．9枚。SLN预测ALN转移准确性为100％，阳性预测值为0。结论 术中用γ探测仪进行乳腺癌SLNB是可行的，SLN可预测腋窝其余淋巴结的转移情况，并可作为早期乳癌患者用SLNB代替ALND的可靠指标。     

Freehand SPECT for image-guided sentinel lymph node biopsy in breast cancer

Purpose

Sentinel lymph node biopsy (SLNB) is standard of care in early-stage breast cancer. Freehand SPECT (FhSPECT) is a system generating 3-D images for intraoperative visual detection of radioactivity in the body. The aim of our study was to evaluate the sensitivity of this technology for sentinel lymph node (SLN) detection and SLNB guidance.

Methods

In 40 patients, FhSPECT was additionally used after planar imaging and probe localization for SLNB. The number of SLNs detected was compared with the number detected by planar scintigraphy (reference method) and the conventional acoustic gamma probe (standard alternative). The sensitivity of FhSPECT was compared with that of the conventional gamma probe (McNemar’s test).

Results

FhSPECT mapped the SLNs in 92.3 % of the basins (36/39) intraoperatively in identical positions to those seen on planar scintigrams. The conventional gamma probe correctly detected the SLNs in 35 of 39 basins (89.7 %). After SLNB, remaining radioactivity was detected by FhSPECT in nine patients, resulting in additional resection of SLNs in four patients.

Conclusion

FhSPECT is a highly sensitive modality for intraoperative detection of SLNs, resulting in the identification of a higher number of SLNs than conventional gamma probe detection.     

Sentinel lymph node biopsy in pregnant patients with breast cancer

Purpose

Sentinel lymph node biopsy (SLNB) is currently not recommended in pregnant patients with breast cancer due to radiation concerns.

Methods

Twelve pregnant patients with breast cancer received low-dose (10 MBq on average) lymphoscintigraphy using ^99mTc human serum albumin nanocolloids.

Results

The sentinel lymph node (SLN) was identified in all patients. Of the 12 patients, 10 had pathologically negative SLN. One patient had micrometastasis in one of four SLN. One patient had metastasis in the SLN and underwent axillary clearance. From the 12 pregnancies, 11 healthy babies were born with no malformations and normal weight. One baby, whose mother underwent lymphatic mapping during the 26th week of gestation, was operated on at the age of 3 months for a ventricular septal defect and at 43 months was in good health. This malformation was suspected at the morphological US examination during week 21, well before lymphoscintigraphy, and was confirmed a posteriori by a different observer based on videotaped material. No overt axillary recurrence appeared in the patients with negative SLNs after a median follow-up of 32 months.

Conclusion

Our experience supports the safety of SLNB in pregnant patients with breast cancer, when performed with a low-dose lymphoscintigraphic technique.     

Clinically node-negative breast cancer, internal mammary lymph nodes, and sentinel lymph node biopsy

We report 2 cases demonstrating that localization of internal mammary (IM) sentinel lymph nodes with lymphoscintigraphy using peritumoral injection of Tc-99m antimony sulfide colloid, followed by resection using minimal access surgery, can reveal nodal metastatic disease in patients with clinically node-negative breast cancer when axillary sentinel nodes are not affected by metastatic disease. When this is found, it changes staging and can affect prognosis and treatment. These cases confirm that the technique used is sampling true sentinel IM nodes, that is nodes that receive direct lymph flow from the breast cancer, and confirm the importance of sampling IM sentinel lymph nodes. Unless techniques are used that are specifically designed to identify IM node drainage from the breast cancer site itself, with subsequent directed surgical removal of sentinel IM nodes, some patients with breast cancer will not be staged correctly.     

乳癌哨兵淋巴结检测临床应用

目的：探讨乳癌哨兵淋巴结活检预测腋窝淋巴结转移状态的可靠性.方法：本组为2000年11月至2004年2月我院收治的140例乳癌患者.术中应用国产亚甲蓝注射液4～6 ml肿瘤上、外、下半圆形皮下连续注射,134例行乳癌改良根治术或患侧乳腺区段切除加腋窝淋巴结清扫术.术后解剖蓝染淋巴管,沿着色淋巴管找到蓝染的哨兵淋巴结.哨兵淋巴结及腋窝淋巴结常规行石蜡病理切片检查.5例行乳腺区段切除加哨兵淋巴结活检,1例行全乳切除加哨兵淋巴结活检（冰冻、石蜡病理检查SLN转移阴性）,未行全腋窝淋巴结清扫.结果：140例患者中136例检出哨兵淋巴结,检出率97.14%,灵敏度 88.71%,准确率94.31%,阴性预测值89.71%,假阴性率11.29%,仅哨兵淋巴结阳性7例.结论：应用亚甲蓝注射液淋巴结着色方法行乳癌哨兵淋巴结活检可以准确地预测腋窝淋巴结转移状态.     

467例乳腺癌患者^99Tc^m-利妥昔单抗前哨淋巴结显像结果分析

目的探讨应用前哨淋巴结（SLN）显像剂^99Tc^m-利妥昔单克隆抗体（简称利妥昔单抗,美罗华）进行乳腺癌SLN活组织检查（SLNB）的可行性与可靠性,以及不同因素对SLN显像及SLNB的影响。方法467例乳腺癌患者在超声引导下于乳腺肿块周围及肿块表面皮下注射^99Tc^m-利妥昔单抗后行SLN显像。术中凭显像结果行腋窝区SLNB,将切取的SLN行常规HE染色及免疫组织化学检查。结果SLN显像成功率99．14％（463／467）,共显示SLN837枚,人均1．79枚（837／467）,分布于腋窝区、内乳区、乳腺组织内及锁骨下区。腋窝区SLNB成功率99．57％（465／467）,手术共探测到SLN1182枚,人均2．53枚。病理检查发现腋窝SLN有转移者131例,转移SLN194枚。其中1例单纯由免疫组织化学法发现微小转移灶。患者年龄、显像时间、病理类型、临床分期、显像前是否行乳腺肿块手术切取活组织检查对SLN显影率、SLNB成功率及SLN转移率均无影响。不同病理类型及临床分期的患者其SLN转移率的差异有统计学意义（χ^2=14．134,29．184,P均〈0．05）。结论应用^99Tc^m-利妥昔单抗行乳腺癌SLN显像及SLNB成功率较高,具有较好的临床应用前景。     

Predicting sentinel lymph node metastasis in breast cancer with lymphoscintigraphy

Objective

Lymphoscintigraphy is an effective method for detecting sentinel lymph nodes (SLNs). However, the rate and degree of SLN detection is not uniform. We quantified SLNs detected with lymphoscintigraphy, and investigated correlations with factors that may influence detection. We then attempted to predict SLN metastasis from lymph node counts, comparing the predictions to subsequent biopsy results.

Methods

We assessed lymph node counts in 100 breast cancer patients in whom a single SLN was detected with a fixed lymphoscintigraphy procedure. We examined correlations between the counts and factors known to influence lymphoscintigraphic SLN detection (age, body mass index, tumor size, and presence or absence of metastasis), and determined reference values (lymph node counts of 10.0, 19.4 and 53.0) which were used to predict SLN metastasis in 100 subsequent patients. The predictions were then compared with the SLN biopsy findings.

Results

SLN counts correlated strongly with the presence or absence of metastasis, with metastasis-positive lymph nodes showing significantly lower counts than negative nodes (p < 0.001). Prediction of SLN metastasis achieved a 100% positive predictive value at a reference value of 10.0, and a 100% negative predictive value at a reference value of 53.0. At a reference value of 19.4, the sensitivity, specificity, and diagnostic accuracy were 77.8, 73.2, and 74.0%, respectively.

Conclusions

The SLN counts detected with lymphoscintigraphy were significantly lower in metastasis-positive lymph nodes than in metastasis-negative lymph nodes. This suggests that prediction of SLN metastasis in breast cancer is possible using lymphoscintigraphy.     

淋巴显像及术中γ探测定位活检乳腺癌前哨淋巴结

目的：探讨淋巴显像及术中γ探测定位活组织检查乳腺癌前硝淋巴结的临床价值。方法：术前在乳腺肿瘤表面正中皮内注射37－74MBq ^99Tcm-大分子右旋糖酐（Dx)，用淋巴显像和术中γ探测定位乳腺癌 前硝淋巴结，术中切除前 淋巴结，而后行腑窝淋巴结清扫术，两标本连同切除的乳腺肿物同时送病理检查，分析和前哨淋巴结转移与腋窝淋巴结的关系。结果：31例均行淋巴显像和术中γ探测定位乳腺癌前哨淋巴结患者中，检出率为100％，有3例前哨淋巴结病理检查呈假阴性，假阴性率为25％，结论：术中γ探测是乳腺癌前哨淋巴结定位最可靠的手段。以乳腺 癌前哨淋巴结活组织检查取代常规腑窝淋巴结清扫术尚需进一步研究。