Staging role of micrometastatic sentinel lymph nodes in breast cancer

AIM: Axillary dissection may be avoided in patients with breast cancer and negative sentinel lymph node (SL); not all metastatic SL patients show metastasis on the remaining axillary lymph nodes. The purpose of this study was to evaluate the possible presence of metastases in the remaining axillary lymphatic glands, the so called not-SL, in patients with SL either macro- or micrometastatic, and to try to locate a subgroup of patients in which metastases are present only in SL. METHODS: A retrospective study was conducted in 91 patients who from March 2000 to June 2003 underwent a biopsy of SL and dissection of the axillary cavity (23 patients with micrometastatic SL and 68 with macrometastatic SL). A multivariate analysis evaluated the statistic association with not-SL metastases of almost 22 prognostic factors. RESULTS: Of the 68 patients affected by macrometastatic SL, 32 (47%) showed metastases of the not-SL; of the 23 patients with micrometastatic SL, 7 (30%) showed metastases of the not-SL. In the last 2 years, among all those patients with micrometastatic SL, the probability of disease at the not-SL reached the null percentage. During year 2000, 3 (50%) patients out of 6 with micrometastatic SL showed metastases at the not-SL; during years 2002/2003 no patients out of 8 with micrometastatic SL showed metastases at the not-SL. A multivariate analysis showed only 2 factors significantly associated to the metastatic not-SL: age (cut off 60 years) OR 4.6, P 0.003 and histological examination of the SL OR 2.8, P 0.003. CONCLUSIONS: The average frequency of disease of not-SL in patients with either micro- or macrometastatic SL is not so different than values observed in literature. The predictive disease value of the remaining axillary lymphatic glands of the micrometastatic SL reached the null percentage in the last 2 years, therefore at seems to depend on the operators experience in SL biopsy technique. Among patients with metastatic SL (micro and macro), it was not possible to detect a subgroup in which not-SL are not metastatic with reasonable certainty. Nevertheless, a multivariate analysis showed the histological factor of the SL, to be significantly associated to not-SL metastases, as well as to the age-factor.     

乳腺癌前哨淋巴结微转移的研究

目的：提高乳腺癌前哨淋巴结（SLN）病理诊断的准确性，为手术彻底切除肿瘤提供依据。方法：应用亚甲蓝生物染色的方法确定60例Ⅰ、Ⅱ期乳腺癌SLN并活检，44（73．3％）例SLN取材成功。每一枚SLN均进行冰冻病理切片、石蜡病理和角蛋白Keratinl9（CK-19）逆转录聚合酶链反应（RT—PCR）检测。结果：44例SLN冰冻病理切片、石蜡病理切片和CK-19诊断的灵敏度和特异度分别是77．8％和100．0％、88．9％和100．0％、100．0％和82．9％，诊断符合率分别为95．5％、97．7％和86．4％，诊断指数分别为0．778、0．889和0．829。结论：CK-19检测可进一步提高乳腺癌SLN微转移的检出率，提高SLN活检的准确性。但CK-19检测与冰冻病理病理检查联合应用可提高诊断的准确率和临床的可操作性。     

A clinical study of immunological status in gastric cancer patients--with special reference to T-cell subsets in the lymphocytes of regional lymph nodes

Non-metastatic regional lymph node lymphocytes of 41 patients with gastric cancer were studied by using different monoclonal antibodies and flow cytometry. Used monoclonal antibodies were OKT3 (total T; CD3), OKT4 (helper/inducer T; CD4), OKT8 (suppressor/cytotoxic T; CD8) and Leu11 (NK/K cell; CD16). The results were as follows: 1. The percentage of CD3 cells and CD4 cells were about ten point fewer in lymph nodes than in peripheral blood. 2. CD8 cells were found to be one half or one third lesser in lymph nodes than in peripheral blood. 3. CD16 cells were found to be rare in lymph nodes. 4. The percentage of CD3, CD4 and CD8 cells were higher in distal lymph nodes than proximal ones. 5. The percentage of CD3, CD4 and CD8 cells were not different with progression of the cancer, whereas CD3 cells and CD8 cells were decreased in lymph nodes of stage IV. 6. The percentage of CD8 cells was higher in distal nodes of stage III. Regional lymph nodes are necessary to protect against cancer metastasis, and killer T cells and cytotoxic T cells were fewer in lymph nodes. These results suggested that killer activity and cytotoxicity of the lymph node lymphocytes are inactive and anergy.     

乳癌前哨淋巴结活检

复习近年来的相关文献，综述乳癌前哨淋巴结活检的技术方法及其临床价值，归纳如下：（1）联合应用染料指示及放射性元素示踪法与单用一种方法相比，前者可提高前哨淋巴结的检出率，降低假阴性率。（2）应用连续切片、免疫组化或逆转录多聚酶链反应方法对前哨淋巴结进行病理学检查，可提高微转移灶的检出，有助于腋淋巴结的准确分期。（3）前哨淋巴结活检操作简单，并发症少，并能准确预测腋淋巴结的状态，可望在部分早期乳癌的治疗中取代腋淋巴结清扫术。     

The nodal neck level of sentinel lymph nodes in mucosal head and neck cancer.

Sentinel node biopsy is emerging as a successful means of identifying subclinical lymph node disease in mucosal head and neck cancer. Sentinel node studies in melanoma and breast cancer have identified sentinel nodes at unusual sites and the technique is redefining our understanding of dynamic lymphatic flow. In this study, the sentinel nodes in mucosal head and neck malignancies were mapped according to their site within the neck and this was correlated with tumour site within the oral cavity. Fifty-two necks were explored for sentinel nodes from tumours located in the tongue (23 cases), floor of mouth (12 cases), palate (six cases), retromolar trigone (five cases), alveolus (three cases), buccal mucosa (two cases), tonsil (two cases) and lip (one case). In total, 124 sentinel nodes were found in levels I-V. Two hot spots were found in the tonsils and were not excised, two nodes were located in level IIB, four nodes were found in level IV, three in the contralateral neck and one in level V. The sentinel nodes located at unusual sites would not have been excised in a supraomohyoid neck dissection and the study has improved our understanding of dynamic lymph flow from tumours.     

What constitutes adequate study of axillary lymph nodes in breast cancer?

This study was undertaken to determine the value of the clearing technique and multilevel sectioning of lymph nodes to aid in optimally examining axillary dissections for lymph node metastases. One hundred consecutive mastectomy specimens with axillary dissections were initially examined by our routine technique: examination of fat for lymph nodes by inspection and palpation and examination of one microsection from each lymph node. The remaining axillary tissue was then cleared using the technique of Durkin and Haagensen and each of the originally examined lymph nodes was resectioned at two additional deeper levels. In our routine examination, 2203 lymph nodes were found with 211 lymph nodes containing metastatic tumor. Clearing disclosed 412 additional lymph nodes, of which 17 contained metastatic tumor. The two additional microsections of lymph nodes revealed tumor in only two lymph nodes which were initially free of tumor. The extended study of the axilla did not add significantly to our routine examination.     

乳腺癌淋巴结微小转移状态下前哨与非前哨淋巴结免疫细胞的改变

目的观察乳腺癌淋巴结微小转移状态下前哨淋巴结(SLN)与非前哨淋巴结(Non- SLN)免疫细胞密度的改变。方法53例符合研究标准的女性乳腺癌患者按SLN不同转移状态分为阴性、游离肿瘤细胞及微转移3组。从各组随机选择6对SLN和Non-SLN与DC-LAMP,CD68,CD123,Foxp3抗体行免疫组织化学染色,半定量评估染色细胞密度改变;所有SLN和Non-SLN蜡块切片均行与DC-LAMP抗体免疫反应的免疫组织学检查以确认成熟树突状细胞(DC)。蔡司图像分析系统定量分析每个淋巴结DC-LAMP阳性细胞的相对密度(DC-LAMP阳性细胞面积/淋巴结面积)。Wicoxon检验和Mann-Whitney检验分别用于DC-LAMP阳性细胞的相对密度的组内和组间比较。结果DC-LAMP阳性细胞密度改变显著。组内比较显示阴性组和微转移组SLN内DC-LAMP阳性细胞平均密度较Non-SLN高(P<0.05);组间比较显示微转移组SLN和Non-SLN内DC-LAMP阳性细胞密度较阴性组显著升高(P<0.05)。结论SLN和Non-SLN内DC-LAMP 细胞平均密度在淋巴结肿瘤转移形成早期发生改变,揭示SLN在肿瘤与引流淋巴结免疫相互作用中起重要作用。     

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目的 研究乳腺癌腋窝淋巴结发生癌转移和未发生癌转移时的免疫功能。方法2004年8月至2005年7月采用流式细胞技术检测乳腺癌病人乳腺癌前哨淋巴结（SLN）与乳腺癌非前哨淋巴结（NSLN）中免疫细胞CD3^＋T、CD4^＋T、CD8^＋T、CD16^＋NK、CD^19^＋B的比例，并相互比较。结果淋巴结未发生癌转移时，SLN与NSLN的免疫细胞CD3^＋T、CD4^＋T、CD8^＋T、CD16^＋NK、CD^19^＋B的比例差异无统计学意义（P〉0．05）；而且当SLN与NSLN发生癌转移后，它们的免疫细胞的比例也无差异。但SLN发生癌转移与未发生癌转移时相比，其CD4^＋T、CD8^＋T、CD16^＋NK的比例发生显著改变（P〈0．05），CD3^＋T、CD19^＋B的比例改变无统计学意义（P〉0．05）。结论 当腋窝淋巴结未发生癌转移时，它仍有正常的免疫功能。当腋窝淋巴结发生癌转移后，它的免疫微环境发生了改变，免疫功能呈现一种抑制状态。     

Intraoperative assessment of sentinel lymph nodes in breast cancer

Background:

Sentinel lymph node biopsy (SLNB) reduces the morbidity of axillary clearance and is the standard of care for patients with clinically node‐negative breast cancer. The ability to analyse the sentinel node during surgery enables a decision to be made whether to proceed to full axillary clearance during primary surgery, thus avoiding a second procedure in node‐positive patients.

Methods:

Current evidence for intraoperative sentinel node analysis following SLNB in breast cancer was reviewed and evaluated, based on articles obtained from a MEDLINE search using the terms ‘sentinel node’, ‘intra‐operative’ and ‘breast cancer’.

Results and conclusion:

Current methods for evaluating the sentinel node during surgery include cytological and histological techniques. Newer quantitative molecular assays have been the subject of much recent clinical research. Pathological techniques of intraoperative SLNB analysis such as touch imprint cytology and frozen section have a high specificity, but a lower and more variably reported sensitivity. Molecular techniques are potentially able to sample a greater proportion of the sentinel node, and could have higher sensitivity. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Management of axillary lymph nodes in breast cancer: a national patterns of care study of 17,151 patients

OBJECTIVE: To determine the rates of axillary lymph node dissection (ALND) and axillary irradiation (AI) in patients with breast cancer and to identify the factors influencing them. SUMMARY BACKGROUND DATA: Routine performance of ALND in the treatment of breast cancer has become controversial. AI has been proposed as an alternative to ALND, and it has been suggested that AI in addition to ALND may decrease local failure in high-risk patients. METHODS: A joint study was conducted by the Commission on Cancer of the American College of Surgeons and the American College of Radiology. A total of 17,151 patients with stage I and II breast cancer treated at 819 institutions in 1994 were studied. RESULTS: A total of 15,992 patients underwent ALND (93%). The mean ages of patients who did and did not undergo ALND were 60.4 and 73.0 years. Univariate analysis demonstrated significantly decreased rates of ALND for women age 70 or older (86% vs. 97%), patients with clinical T1 a tumors (81% vs. 93%), grade I histology (90% vs. 95%), and patients with favorable tumor types (88% vs. 94%). The ALND rate did not vary between palpable and nonpalpable tumors. Multivariate analysis of variables affecting the rate of ALND identified type of surgery, age, tumor size, histology, and payer status as significant. A total of 889 patients received AI. Patients not undergoing ALND were more likely to receive AI (10% vs. 5%). A total of 1.6% of patients with no lymph node metastasis underwent AI, 8.9% of those with one to three positive nodes underwent AI, 24.0% of those with four to nine positive lymph nodes underwent AI, and 29.9% of those with > or = 10 positive lymph nodes underwent AI. Multivariate analysis of variables affecting the proportion of patients who received AI and had undergone ALND identified nodal status and type of surgery as significant. CONCLUSIONS: Axillary lymph node dissection continues to be routinely applied in the treatment of breast cancer, and AI remains underused in patients at high risk for local regional relapse.     

Predictors of positive axillary lymph nodes after sentinel lymph node biopsy in breast cancer.

OBJECTIVE: The purpose of this study was to determine the factors that predict the presence of metastasis in nonsentinel lymph nodes (SLN) when the SLN is positive. METHODS: A prospective database was analyzed and included patients who underwent SLN biopsy for invasive breast cancer from July 1997 to August 2000 (n = 442). One hundred (22.6%) patients had one or more positive SLNs, and were analyzed to determine factors that predicted additional positive axillary nodes. RESULTS: Of the 100 patients with a positive SLN, 40 patients (40%) had additional metastasis in non-SLNs. The only significant variables that predicted non-SLN metastasis were tumor lymphovascular invasion (P = 0.004), extranodal extension (P < 0.001), and increasing size of the metastasis within the SLN (P = 0.011). In analyzing just those patients who had lymphovascular invasion, extranodal extension, and a SLN metastasis > 2mm, 92% were found to have additional positive nodes. CONCLUSIONS: In patients with invasive breast cancer and a positive sentinel lymph node, lymphovascular invasion, extranodal extension, and increasing size of the metastasis all significantly increase the frequency of additional positive nodes.     

乳腺癌腋窝淋巴结外科处理及其解剖学基础

解剖学是所有外科手术的基础.毫无疑问,解剖学的不断发展,促进了手术技术的进步,手术方式也出现相应的变化.随着相关疾病生物学特性认识的深入、外科治疗理念的进步以及非手术治疗手段的丰富,推动了外科手术方式的变革,使其更趋合理、更加人性化.