乳腺癌内乳淋巴结活检的临床研究

背景与目的:内乳淋巴结(intemal mammary node,IMN)是乳腺癌重要的转移途径之一,其状况将影响乳腺癌患者的分期、治疗、预后及疗效评价,本研究旨在探讨内乳前哨淋巴结活检(intemal mammary sentinel node biopsy,IMSNB)和经肋间IMN第Ⅰ～Ⅳ肋间活检、以及IMN微转移灶检测在临床应用的意义.方法:在行常规乳腺癌切除术中,采用核素示踪法经肋间隙行IMSNB,然后对患侧第Ⅰ～Ⅳ肋间的IMN均行活检(经肋间隙,非扩大根治术),所有IMN均行常规单一切面HE染色病理检查,阴性病例的IMN采用多层切片加免疫组化的方法检测微转移.结果:全组38例病人中发现内乳前哨淋巴结(internal mammary sentinel node,IMSN)17例,占44.7%,均成功行IMSNB,其中4例IMSN常规病理阳性,1例IMSN发现微转移,2例发现孤立的肿瘤细胞群,10例为阴性,均与对应病例经第Ⅰ～Ⅳ肋间IMN活检的病理结果一致;无发现IMSN 21例,占55.3%,经第Ⅰ～Ⅳ肋间IMN活检,常规病理阳性5例,阴性16例,未发现微转移.结论:对发现IMSN者,IMSN能够准确评价IMN状况,但对无发现IMSN者,尤其是对IMN转移可能性大者,应经肋间隙行IMN第Ⅰ～Ⅳ肋间活检,以减少假阴性的发生;多层切片加免疫组化技术有助于IMN微转移灶的检出.     

Internal mammary lymph node (IMN) coverage by standard radiation tangent fields in patients showing IMN drainage on lymphoscintigraphy: therapeutic implications

The purpose of this report is to evaluate the variability in coverage of the internal mammary nodal chain (IMN) by standard radiation tangential fields in those patients with medial drainage on lymphoscintigraphy. Twenty-two patients who showed lymphoscintigraphic IMN drainage underwent radiation simulation planned with computed tomography (CT). Standard tangent fields were placed and CT scans were reviewed to assess IMN inclusion and correlation with presternal fat thickness. Of the 22 patients who showed IMN drainage on lymphoscintigraphy, 10 (45%) had lateral primary lesions, 9 (41%) had medial lesions and 3 (14%) had subareolar lesions. Of these 22 women, 4 (19%) had the IMN completely within the standard tangent fields. Twelve women (55%) had only partial coverage of the IMN and the remaining 6 women (27%) had the IMN region completely outside. Presternal fat thickness greater than 10 mm was less likely associated with complete IMN coverage than fat thickness 10 mm or less, P = 0.001. Lymphoscintigram drainage to the IMN in breast cancer patients may suggest an increased risk of IMN involvement. Our data show that a majority (73%) of these patients had complete or partial incidental inclusion of the IMNs with standard tangents, which may in part explain the historically low IMN failure rate.     

Internal mammary chain sentinel lymph node identification in breast cancer

BACKGROUND AND OBJECTIVES: Sentinel lymph node (SLN) biopsy is not usually performed with respect to the internal mammary lymph node chain. However, the SLN may be located in the internal mammary chain, particularly with medial lesions. We carried out this study to investigate whether lymphatic mapping and SLN biopsy can detect internal mammary involvement in patients with breast cancer. METHODS: A dye- and gamma probe-guided SLN biopsy was performed in a consecutive series of 41 patients with tumor in situ or clinical stage I or II breast cancer. After the biopsy, these patients underwent either a modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection. Biopsy of internal mammary lymph nodes was performed in 19 of these patients. RESULTS: No involvement of internal mammary lymph nodes was found histologically in 5 patients in whom lymphatic flow or a "hot nodule" in the internal mammary chain was found using lymphoscintigraphy. Nodal involvement was demonstrated histologically in only 1 of 5 cases where lymphatic vessels showed dye staining or faintly stained nodes. Internal mammary lymph node biopsy also was performed in 14 of 36 patients with neither stained lymphatic vessels or nodes, nor with lymphatic flow or a hot nodule by lymphoscintigraphy. Nodal involvement was found histologically in 1 of these patients. CONCLUSION: SLN biopsy guided by lymphatic mapping is unreliable for identifying metastases to internal mammary lymph nodes.     

Internal mammary node drainage and its role in sentinel lymph node biopsy: the initial ALMANAC experience

This study was designed to identify the frequency of internal mammary drainage in patients undergoing sentinel lymph node (SLN) lymphoscintigraphy in a controlled clinical trial. The practicability and relevance of internal mammary SLN biopsy as a method to improve nodal staging and treatment in breast cancer were investigated. A total of 707 evaluable patients with invasive breast cancer underwent SLN biopsy based on lymphoscintigraphy, intraoperative g probe detection, and blue dye mapping using technetium Tc 99m albumin colloid and Patent Blue V injected peritumorally. This was followed by standard axillary treatment in the same operation in all patients. Lymphoscintigraphy showed internal mammary sentinel nodes in 62 patients (9%), and internal mammary drainage was identified perioperatively in an additional 7 patients (1%) using g probe detection. Sampling of the internal mammary basin, based on the results of lymphoscintigraphy and g probe detection, was done in 31 of 69 patients (45%). One patient had a pneumothorax and 2 experienced bleeding during internal mammary sampling. Internal mammary metastases were detected in 4 of 31 patients (13%). In 2 of the patients (6%), internal mammary nodes (IMNs) showed metastatic involvement without accompanying axillary metastases. One of these 2 patients would have received adjuvant endocrine systemic therapy because of the characteristics of the tumor, but may not have been recommended to receive adjuvant chemotherapy. Sampling of the internal mammary basin led to a change of management in these 2 patients, ie, institution of adjuvant chemotherapy. Therefore, a change in management occurred in only 2 of the 69 patients in our series, but 38 patients with unbiopsied "hot" IMNs remained with unknown internal mammary status. Biopsy of IMNs alters staging in few patients, and the impact on indication for adjuvant treatment was low. Internal mammary SLN biopsy may be associated with some additional morbidity. Current evidence suggests that internal mammary SLN biopsy is still a research tool.     

Internal mammary lymph node recurrence: rare but characteristic metastasis site in breast cancer

Background  

To assess the frequency of IMLN recurrence, its associated risk factors with disease-free interval (DFI) and its predicting factors on overall survival time.     

Internal mammary lymph nodes and sentinel node biopsy in breast cancer.

The long-term follow-up of patients treated with extended radical mastectomy has proved that the internal mammary node (IMN) status is an important prognosticator of breast cancer. Patients with isolated IMN involvement seem to have the same outcome as those with limited axillary disease, and these patients may therefore be overstaged in the TNM system. Sentinel node biopsy (SNB) of IMNs may be an ideal staging procedure, but lymphatic mapping studies demonstrate that data from extended radical mastectomy series cannot be extrapolated to patients suitable for SNB, where the IMN involvement is <5% overall, and around 1% for IMN metastases without axillary disease. Current evidence does not allow internal mammary SNB to be recommended as a standard procedure, but as patients with IMN involvement may benefit from adjuvant systemic treatment, internal mammary SNB should be further studied in this context.     

乳腺癌新辅助化疗后内乳区前哨淋巴结活检研究

目的：新辅助化疗（neoadjuvant chemotherapy,NAC）目前已成为局部晚期乳腺癌患者的标准治疗模式。本研究旨在评估乳腺癌患者在NAC后接受内乳区前哨淋巴结活检（internal mammary sentinel lymph node biopsy,IMSLNB）的临床获益。方法：回顾性分析2014年4月—2018年4月山东大学附属山东省肿瘤医院乳腺病中心收治的202例接受NAC的原发性乳腺癌患者的临床资料并进行统计分析,入组患者术前均采用“新型注射技术”注射核素示踪剂。术前哨位淋巴结显像和（或）术中γ探测仪发现内乳区前哨淋巴结（internal mammary sentinel lymph node,IMSLN）显像者行经肋间IMSLNB。根据目前的指南评估NAC后接受IMSLNB的临床获益。结果：入组202例患者,NAC后IMSLN显像率为34.2%(69/202),且与临床肿瘤分期相关（P=0.017）,IMSLN显像患者中,临床淋巴结阴性和临床淋巴结阳性（clinical lymph node-positive,cN⁺）患者分别占11.6% (8/69)和88.4%(61/69)。NAC后IMSLNB的成功率为98.6%（68/69）,IMSLN的检出率为33.7%(68/202),转移率为11.8% (8/68),8例IMSLN转移患者,术后淋巴结分期发生了改变,其中1例患者不伴腋窝淋巴结（axillary lymph node,ALN）转移（pN₀至pN_1b）,2例伴1~3枚ALN转移（pN_1a至pN_1c）,4例伴4~9枚ALN转移（pN_2a至pN_3b）,1例伴≥10枚ALN转移（pN_3a至pN_3b）,术后病理学分期也发生了改变（0期至ⅠB期,ⅡA/ⅢA期至ⅢC期）,这8例IMSLN转移患者术后均接受了内乳区放疗（internal mammary node irradiation,IMNI）。结论：NAC后IMSLN有显像的患者,尤其是cN⁺患者,NAC后应接受IMSLNB,以期获得完整的淋巴结分期。IMSLNB能够进一步完善淋巴结病理完全缓解的定义并指导IMNI。     

Internal mammary node metastasis in breast cancer: Predictive models to determine status & management algorithms

Aim

Internal mammary node (IMN) metastases are an important prognostic factor in breast cancer. However due to difficulty of access, most surgeons ignore these nodes, hence adjuvant treatment decisions may be compromised. Through mathematical modeling based on large datasets this study aims to estimate the current rate of IMN and sentinel node metastasis.

Methods

Models were created to estimate the current rate of axillary and IM sentinel node metastasis. Data from historical extended radical mastectomy series were analyzed to project contemporary rates of IMN metastasis. This information was coupled with derived models and contemporary datasets: a single-institution breast lymphoscintigraphy database (1992–2007) to establish lymphatic anatomy; and the Surveillance, Epidemiology and End-Results (SEER) registries in the US (2000–2003).

Results

Rates of IMN metastasis and positive sentinel nodes were estimated and models derived to assist with predicting IMN status in patients. If high definition peritumoral lymphatic mapping were available, the predicted rates of positive sentinel nodes in the axilla (AN) and internal mammary chain (IMN) would be equal. We predicted the overall rate of IMN metastasis is ∼39% the rate of positive sentinel AN.

Conclusion

Simplified models and algorithms can predict IMN status.     

乳腺癌胸腔镜内乳淋巴结清扫的临床分析(附52例报告)

目的探索胸腔镜内乳淋巴结清扫在乳腺癌分期和治疗中的作用。方法收集中山大学肿瘤防治中心2001年11月至2006年11月住院的病灶位于乳腺内侧或中央区的乳腺癌患者52例，常规乳腺癌切除术后行胸腔镜内乳淋巴结清扫，分析术后病理分期的改变，计算术后的无病生存率。结果52例患者中内乳淋巴结转移20例，占38．5％。其中单纯内乳淋巴结转移6例，占11．5％；腋窝淋巴结转移1～3枚且内乳淋巴结有转移的5例，占9．6％；腋窝淋巴结转移4～9枚且内乳淋巴结有转移的3例，占5．8％，腋窝淋巴结转移≥10枚且内乳淋巴结有转移的6例，占11．5％。共有20例（占38．5％）乳腺癌患者在胸腔镜内乳淋巴结清扫术后区域淋巴结分期发生改变。术后1年无病生存率100％，2年无病生存率94．3％，3年无病生存率86．2％。结论胸腔镜内乳淋巴结清扫不仅可帮助明确乳腺癌的病理分期，以指导治疗，而且对于中央区和内侧病灶的乳腺癌患者还可能降低局部复发率。     

临床腋窝淋巴结阳性乳腺癌患者内乳区前哨淋巴结活检术研究*

目的：评估临床腋窝淋巴结阳性乳腺癌患者行内乳区前哨淋巴结活检术（IM-SLNB）的临床意义。方法：2013年6 月至2014年10月对山东省肿瘤医院乳腺病中心就诊的64例临床腋窝淋巴结阳性的原发性乳腺癌患者行前瞻性单臂入组研究,采取腋窝淋巴结清扫术,同时均应用新的核素注射技术进行IM-SLNB。结果：64例患者中内乳区前哨淋巴结（IM-SLN）显像为38例,显像率为59.4%（38/ 64）。 38例IM-SLN 显像患者中IM-SLNB 成功率为100%（38/ 38）,并发症发生率为7.9%（3/ 38）,IM-SLN 转移率为21.1%（8/ 38）。 肿瘤位于内上象限和腋窝淋巴结转移数目较多的患者,其IM-SLN 转移率较高（P < 0.001 和P = 0.017）。 患者临床获益率为59.4%（38/ 64）,其中12.5%（8/ 64）另接受了内乳区放疗、46.9%（30/ 64）避免了不必要的内乳区放疗。结论：临床腋窝淋巴结阳性的乳腺癌应进行IM-SLNB,尤其对于肿瘤位于内上象限及怀疑存在较多腋窝淋巴结转移数目的患者,以获得内乳区淋巴结的转移状态,指导乳腺癌患者内乳区放疗。     

乳腺癌乳房切除术后放疗患者内乳淋巴引流区非计划性受照剂量影响因素探讨

目的 探讨乳腺癌乳房切除术后放疗患者内乳淋巴引流区(IMN)非计划性照射时IMN受照剂量的影响因素。 方法 回顾性分析我院 138例乳腺癌根治术后接受胸壁 ±锁骨上下淋巴引流区放疗(3DCRT、正向IMRT或逆向IMRT)患者资料,依据RTOG标准勾画患侧IMN,获取IMN非计划性受照剂量。分析患者IMN非计划性照射时IMN受照剂量与患者临床特征及放疗技术特定参数的相关性。 结果 IMN非计划性受照剂量平均为32.85 Gy (2.76~50.93 Gy),7.3%患者达到了治疗剂量(≥45 Gy),且达到治疗剂量组的患者体重、体重指数、体表面积以及胸廓横径(DT)指标均低于未达到治疗组的患者,而包含在胸壁PTV内的内乳PTV体积(IMNin)及IMNin占IMN计划靶区体积的比例(RIMNin)要高于未达到治疗组的患者。多元线性回归分析结果显示,患者体重、胸廓前后径(DAP)、DT、RIMNin及PTV体积均是IMN非计划性受照剂量的影响因素(P=0.000、0.000、0.001、0.000、0.034)。 结论 乳房切除术后放疗的患者,IMN作为非计划靶区时,其受照剂量变化范围较大,部分患者可以达到治疗剂量,而且IMN非计划受照剂量受到患者某些体质特征、解剖学特征及放疗技术参数的影响,在进行相关研究设计或研究结果分析时对此应予以足够重视。     

Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer

PURPOSE: To compare outcome for ipsilateral breast tumor recurrence (IBTR), or regional node recurrence, initial and subsequent distant metastases, and overall and cause-specific survival in women treated with conservative surgery and radiation based on whether or not radiation was targeted to the internal mammary nodes (IMN). METHODS AND MATERIALS: From 1979-1994, 1383 women with Stage I-II breast cancer underwent wide excision, axillary node dissection with >/=10 nodes removed, and radiation. Median follow-up was 6 years; median age was 55 years. A total of 114 women had radiation targeted to the IMN with deep tangents and 1269 did not. Women who received IMN treatment were more often axillary node-positive (40% vs. 25%, p = 0. 002), had central or inner quadrant tumors (61% vs. 40%, p = 0.001), and had T2 tumors (47% vs. 31%, p = 0.001). All axillary node-positive women received adjuvant chemotherapy and/or tamoxifen. For axillary node-negative women, 13% of the IMN treatment group received adjuvant systemic therapy compared to 37% of the no treatment group (p = 0.001). Radiation was directed to the breast only in 97% of the axillary node-negative women who had IMN treatment and 99% of the no IMN treatment group. For axillary node-positive women, 98% of the IMN-treated group had radiation to the breast and supraclavicular nodes +/- a posterior axillary field compared to 77% of the no IMN treatment group (p = 0.001). There were no significant differences between the two groups for median age, menopausal status, histology, final surgical margin, estrogen and progesterone receptor status, or the number of positive nodes. RESULTS: There were no significant differences in the 5- and 10-year cumulative incidence of an IBTR, regional node recurrence, initial or total distant metastases for the two groups. Similarly 5- and 10-year actuarial overall and cause-specific survival were not significantly different. However, subset analysis revealed a statistically significant increase in initial (29% vs. 15% at 10 yr, p = 0.002) and total (30% vs. 17% at 10 yr, p = 0.01) distant metastases and a significant decrease in cause-specific survival (76% vs. 89% at 10 yr, p = 0.02) for postmenopausal women who received IMN treatment. These findings could not be attributed to differences in the use of systemic therapy or the number of positive nodes. Axillary node-positive patients did not experience a significant decrease in initial (36% vs. 22% at 10 yr, p = 0.21) or total distant metastases (37% vs. 28% at 10 yr, p = 0.62) or a significant improvement in cause-specific survival (72% vs. 76% at 10 yr, p = 0.76) with IMN treatment regardless of whether the tumor was lateral or medial/central in location. IMN treatment was not associated with an increase in non-breast cancer deaths during this period of observation. CONCLUSIONS: This retrospective series was unable to identify a significant benefit for IMN irradiation in terms of distant metastases or cause-specific survival for the entire patient population, and in particular, for patients with positive axillary nodes and medially located lesions. The results of the proposed or ongoing prospective randomized trials will further address this controversial issue.     

Regional node dissection for melanoma: techniques and indication

Because virtually all microscopic nodal disease left untreated in melanoma patients will progress to clinically apparent macroscopic nodal disease, there is worse prognosis with macroscopic nodal disease, and ineffective systemic treatment currently exists, one must be cautious in favoring an observation approach to the regional basin in patients with a positive sentinel lymph node (SLN) in the hopes of avoiding the potential morbidity of a therapeutic node dissection. In the few patients with untreated microscopic nodal disease, the prognosis will be significantly worsened. Until further data are available, melanoma patients with a positive SLN by H&E analysis should proceed to a complete lymph node dissection.     

内乳淋巴结清扫术后患者内乳靶区不同勾画方法比较研究

目的 以内乳淋巴结清扫(ImlND)前勾画的内乳淋巴结临床靶区(CTVImlN)为参照,对比不同勾画方法构建的ImlND术后CTVImlN靶区间差异,探讨ImlND后CTVImlN勾画的合理方法。方法 选取已行患侧ImlND且术前、术后CT图像资料完整的乳腺癌改良根治术(MRM)患者 20例。依据RTOG指南在术前CT图像上勾画健侧及患侧CTVImlN (CTVpr-I、CTVpr-a)。在术后CT图像上分别采用形变配准(DIR)法、视觉对照法、精确测量法勾画术后患侧CTVImlN,并分别命名为CTVDIR、CTVV、CTVM。比较CTVV、CTVM、CTVDIR与CTVpr-a间靶区中心间距、靶区体积以及3种不同方式构建的CTVImlN的适形指数(CI)及包含度(DI)差异。结果 CTVV、CTVM、CTVDIR与CTVpr-a的靶区中心间距分别为2.17、1.44、1.25cm。CTVpr-a、CTVpr-I、CTVV、CTVM和CTVDIR的靶体积分别为2.10、2.17、2.04、1.88、2.07cm³(均 P>0.05)。CTVV-CTVpr-a间、CTVM-CTVpr-a间CI均为0.16,CTVDIR-CTVpr-a间CI为0.43,明显高于前两者(均 P<0.01)。CTVV-CTVpr-a、CTVM-CTVpr-a间DI分别为0.26和0.24,CTVDIR-CTVpr-a间DI为0.58,明显高于前两者(均 P<0.01)。结论 准确勾画ImlND术后的CTVImlN是困难的,但相比较而言,DIR法所勾画靶区的空间位置适配度优于视觉对照法和精确测量法。     

乳腺癌根治术后内乳淋巴结首先复发的特点

目的 分析乳腺癌患者经根治术及辅助治疗后以内乳淋巴结为首先复发的临床表现和特点，总结其误诊的有关因素。方法 对31例女性乳腺癌患者进行多项分析，包括患者原发乳腺癌的发病和治疗情况、内乳复发病灶的特点、确诊手段、误诊以及对挽救治疗的影响等。本组患者占同期收治乳腺癌女患者的0．6％，手术时年龄29－60岁（中位44岁）。根治术后16例未做正规辅助治疗，11例仅做辅助化疗或内分泌治疗，4例做了内乳放射结合化疗或内分泌治疗。结果 术后到确诊内乳复发的时间为8－132个月（中位34个月）。复发病灶均表现为胸骨旁隆起或肿块（直径2－10cm，中位5cm），伴胸痛、皮肤受累和胸骨破坏，其百分比例分别为61．3％、35．5％和64．5％；45．2％的病变跨多个肋间隙，病变中心位于3个肋间的比例为90．0％。误诊包括胸骨转移（22例）、胸壁复发（10例）、肋软骨炎症（5例）等。挽救治疗均包括放射治疗、综合局部切除或全身治疗。内乳淋巴结转移确诊治疗后的3、5和10年生存率分别为60．0％、26．1％和12．9％。复发病灶直径≥6cm的患者较病灶直径＜6cm的患者生存时间明显缩短（P＜0．05），推测可能与治疗延误有关。结论 乳腺癌多数的内乳淋巴结复发位于3个肋间。内乳淋巴结复发常被误诊为胸骨转移、胸壁复发、肋软骨炎症等。误诊导致的治疗延误和不当有可能影响预后。