Local administration of liposomal adriamycin inhibited proliferation of metastatic cells in axillary lymph nodes in rabbit breast cancer model

Objective： To assess the inhibitory effects of liposomal adriamycin （LADR） locally injected into mammary glands of VX2 tumor-bearing rabbits on proliferation of lymph nodal metastatic cells. Methods： Twenty-one VX2 tumor-bearing rabbits were randomly and equally divided into 3 groups. Rabbits were randomized to receive sham treatment （Group I）, subcutaneous LADR around tumor （Group Ⅱ） and intravenous free adriamycin （Group Ⅲ）, respectively. Breast tumor and axillary lymph nodes were harvested after 3 repeated treatment. Nodal sizes of both pre-and post-treatment were measured. Proliferating cell nuclear antigen （PCNA） mRNA in both tumor and lymph nodes were determined by RT-PCR. Results： The mean size of axillary lymph nodes in Group I, Ⅱ and Ⅲ increased by 3.70%, 1.55% and 2.89%, respectively, with significant difference between Group Ⅲ and I （P=-0.004） and between Group Ⅱ and Ⅲ（P=-0.002）. Relative expression values of PCNA mRNA in breast tumors of Group I, Ⅱ and Ⅲ were 0.486, 0.513 and 0.396, respectively. For Group Ⅲ, PCNA mRNA was significantly less expressed than that in Group I （P=-0.023） and Ⅱ（P=0.005）. Relative expression values of PCNA mRNA in axillary lymph nodes of Group I, Ⅱ and Ⅲ were 0.541, 0.329 and 0.450, respectively. Compared with Group I, Group Ⅲ showed a markedly decreased expression of PCNA （P=-0.021）. The least level ofPCNA mRNA was found in Group Ⅱ, with a significant difference from that in Group Ⅲ（P=-0.004）. Conclusion： Local injection of LADR was an effective therapeutic regimen for lymphatic metastases from breast cancer, regardless of its little effect on primary tumor.     

阿霉素纳米脂质体不同途径给药治疗晚期兔VX2乳腺移植癌模型

目的研究阿霉素纳米脂质体（NLADR）经不同途径给药对晚期兔乳腺癌模型的治疗效果。方法pH梯度载药法制备NLADR,平均粒径120nm。50只雌性新西兰兔随机分为5组,每组10只,组织块悬液注射法制备VX：乳腺移植癌模型,植瘤后第6周开始治疗。A组：对照组,不给予特殊治疗;B组：肿瘤周围皮下注射NLADR;C组：经耳缘静脉注射NLADR;D组：同时给予NLADR静脉、局部注射,药量各占1／2;E组：经耳缘静脉注射阿霉素水溶液（FADR）。B、C、D、E组单次药物剂量1mg／kg,每48h重复给药1次,3次治疗后48h处死动物,切除移植瘤、腋窝淋巴结及所有发现的远处转移灶,测量治疗前后移植瘤、腋窝淋巴结体积变化,病理切片观察癌灶坏死情况,逆转录-聚合酶链反应（RT—PCR）检测肿瘤细胞增殖细胞核抗原（PCNA）,末端标记技术（TUNEL）检测癌细胞凋亡。结果静脉注射NLADR、FADR对移植瘤和肺肝转移灶均表现出明显的抑制,局部注射NLADR对腋窝、纵隔淋巴结的癌转移灶有显著疗效,静脉联合局部注射NLADR对乳腺肿瘤、淋巴结、肺肝转移灶均有显著疗效,癌细胞大量坏死或凋亡,PCNA mRNA表达降低,肿瘤及腋窝淋巴结的增长减缓。结论NLADR静脉与局部给药相结合,对伴有局部淋巴结和远处器官转移的晚期乳腺癌有显著的治疗效果。     

CT间接淋巴造影诊断舌癌颈淋巴结早期转移

目的：探讨舌癌的早期转移颈淋巴结在CT间接淋巴造影中的特点。方法：健康成年新西兰白兔18只,随机法分成3组,颈淋巴结正常组、增生组及早期转移组各6只;分别于注射前及在舌腹黏膜下注射0.5 mL欧乃派克后1、5、15、20 min行轴位CT扫描,观察3组淋巴结在间接淋巴造影时的不同特点。结果：所有动物在造影整个过程中颌下淋巴结及颈浅淋巴结均未显影,而只有颈深淋巴结在所有动物中均显影,整个显影过程中未见有明显的血管显影。在CT上转移组淋巴结的平均直径为（0.73±0.08）cm,增生组为（0.75±0.10）cm,而正常组为（0.47±0.05）cm,正常组淋巴结大小分别与转移组和增生组淋巴结大小比较差异有统计学意义。转移组淋巴结内造影剂消退缓慢,而增生组及正常组淋巴结内造影剂消退较快;转移组淋巴结表现为充盈缺损、周边凹凸不平、质地不均、毛糙,而增生组及正常组淋巴结质地均匀,周边光滑,无充盈缺损。结论：CT间接淋巴造影对舌癌颈淋巴结早期转移的诊断有一定的特异性,这些特异性有可能作为诊断早期转移淋巴结的指标。     

乳腺癌中survivin蛋白的表达和PCNA及腋窝淋巴结转移的关系

目的 探讨乳腺癌中survivin蛋白的表达及其与肿瘤细胞增殖和腋窝淋巴结转移的关系。方法 收集乳腺癌74例，其中有腋窝淋巴结转移的34例，用免疫组化染色检测survivin和增殖细胞核抗原(Proliferating cell nuclear antigen,PCNA)蛋白的表达情况。结果 ①乳腺癌组织中有survivin蛋白的表达，其阳性表达率为64．9％。②survivin蛋白表达阳性的乳腺癌细胞PCNA的标记指数明显高于survivin蛋白表达阴性者。③无腋窝淋巴结转移的乳腺癌中survivin蛋白阳性表达率明显低于有腋窝淋巴结转移者。结论 乳腺癌组织中有survivin蛋白的表达，且其表达与肿瘤细胞增殖和腋窝淋巴结转移有关。     

前哨淋巴结活检术辅助手术治疗乳腺癌及对腋窝淋巴结分期的预测作用

目的探究前哨淋巴结活检术(SLNB)辅助手术治疗乳腺癌及对腋窝淋巴结分期的预测效果。方法选取2018年1月至2020年12月本院收治的82例乳腺癌患者作为研究对象,随机分为两组,各41例。对照组采用腋窝淋巴结清扫术与乳腺全切术治疗,观察组根据前哨淋巴结活检术病理结果确定是否对患者实施腋窝淋巴结清扫术治疗。比较两组手术时间、住院时间、血清肿瘤标志物及并发症发生率,并探究前哨淋巴结活检术对淋巴分期的预测价值。结果观察组手术时间、住院时间均短于对照组,差异有统计学意义(P<0.05)。治疗前,两组血清肿瘤标志物水平比较差异无统计学意义;治疗后,观察组血清肿瘤标志物水平均低于对照组,差异有统计学意义(P<0.05)。观察组并发症发生率为12.20%,低于对照组的39.03%,差异有统计学意义(P<0.05)。观察组前哨淋巴结活检检出率为97.56%(40/41),在每例患者中发现1~3枚前哨淋巴结,前哨淋巴结共57枚。通过开展HE染色和连续切片,发现前哨淋巴结阳性率为41.46%(17/41),其中微转移4例。结论乳腺癌患者开展手术治疗前行前哨淋巴结活检术,能有效评估腋窝淋巴结情况,准确判断是否开展腋窝淋巴结清扫术,降低患者术后并发症发生率,缩短手术时间与住院时间,促进机体恢复。     

亚甲蓝示踪法定位乳腺癌前哨淋巴结的评价

目的 评估亚甲蓝在乳腺癌前哨淋巴结活检（SLNB）中的应用价值。方法 对100例临床分期为T1-2N0M0的乳腺癌患者，术中用1%亚甲蓝注射在原发肿瘤周围进行腋淋巴结定位并前哨淋巴结切除；随即行乳腺癌根治或改良根治切除术，全部标本作病理学检查。结果 本组100例患者中78例发现了前哨淋巴结（SLN），占78%，发现前哨淋巴结的患者中40例（51.2%)有腋窝淋巴结癌转移，其中有3例SLN阴性，用亚甲蓝为示踪剂SLNB的准确率为96.1%(75/78)，假阴性率为7.5%(3/40)；SLN对腋窝淋巴结状况预测的敏感性为92.5%(37/40)；阳性预测值和阴性预测值分别为100%和90.2%。结论 亚甲蓝示踪法在探查乳腺癌前哨淋巴结估测癌转移，指导根治切除术范围具有临床应用价值。     

乳腺癌和腋窝淋巴结转移癌组织中COX-2的表达及意义

目的：研究环氧化酶-2（COX-2）在乳腺癌原发灶和腋窝淋巴结转移灶中的表达并探讨其临床意义。方法：应用免疫组织化学S-P法检测9例癌旁正常乳腺组织、50例乳腺癌原发灶、19例腋窝阳性淋巴结和31例腋窝阴性淋巴结中COX-2的表达。结果：在乳腺癌原发灶和腋窝淋巴结转移灶中COX-2呈阳性表达,棕黄色颗粒弥漫分布于癌细胞的细胞浆内,在正常乳腺组织中棕黄色颗粒弥漫分布于间质细胞中,在非转移淋巴结棕黄色颗粒弥漫分布于淋巴结部分巨噬细胞的细胞浆内。COX-2在正常乳腺组织、原发癌组织、腋窝阳性淋巴结和腋窝阴性淋巴结中的阳性表达率分别为11.1%、60.0%、84.2%和32.3%,正常乳腺组织、原发癌组织、腋窝阳性淋巴结三者间COX-2的表达率比较差异有显著性(P<0.01),阴性淋巴结（32.3%）与阳性淋巴结（84.2%）之间COX-2的表达差异有显著性(P<0.001)。COX-2在淋巴结阳性原发癌组织（84.2%）和淋巴结阴性原发癌组织（45.2%）中的表达率比较差异有显著性(P<0.01)。结论： COX-2阳性表达的患者可能易发生乳腺癌腋窝淋巴结转移。     

Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles in detecting lymph node metastasis of tumors: an experimental study]

OBJECTIVE: To investigate the value of superparamagnetic iron oxide particles (SPIO) in magnetic resonance (MR) imaging for detecting lymph node metastasis of tumors. METHODS: Twelve New Zealand rabbits were used in this study, 6 of which received unilateral intra-muscular inoculation of VX2 carcinoma cells to induce lymph node metastasis of the tumor, and the other 6 served as normal control group. MR images of the lymph nodes of the rabbits were obtained before and 12 h after subcutaneous injection of SPIO, followed by image analysis in correlation with pathological examinations. RESULTS: On plain MR images, normal and metastatic lymph nodes showed similar signal characteristics. After administration of SPIO, the signal intensity of both normal lymph nodes and metastatic ones remained unchanged in spin echo (SE) T1-weighted images. On SE T2-weighted images, the signal intensity of normal lymph nodes significantly decreased heterogeneously, while that of all metastatic lymph nodes remained unchanged. In gradient recalled echo (GRE) T2-weighted images, the signal intensity of normal lymph nodes decreased significantly and homogeneously, while that of 4 rabbits in metastasis group remained unchanged, with the signal intensity in the other 2 rabbits decreased heterogeneously. CONCLUSION: SPIO-enhanced MR imaging can be applied to detect lymph node metastasis of the tumors.     

Kodama法淋巴结清扫在乳腺癌Auchincloss术中的应用

目的:探讨Kodama法在乳腺癌Auchincloss术中清扫LEVELⅢ淋巴结的可行性及意义。方法:对68例女性初治可手术乳腺癌患者,在Auchincloss术基础上,加行Kodama法清扫LEVELⅢ淋巴结,并单独标记送病检,对该组淋巴结转移率及临床相关因素进行统计学分析。结果:LEVELⅢ淋巴结转移率为30.88%。与LEVELⅢ淋巴结转移阳性率差异均无统计学意义的因素有患者的年龄、病理类型和肿瘤数目(P>0.05);与LEVELⅢ淋巴结转移阳性率差异均有统计学意义的因素有肿瘤的大小、患侧腋窝淋巴结状态、TNM分期和分子分型(P<0.05)。结论:对淋巴结转移高危因素乳腺癌患者行Auchincloss术时,加行Kodama法清扫腋窝LEVELⅢ淋巴结是必要且安全可行的。     

美兰染料法示踪乳腺癌前哨淋巴结66例

目的 探讨使用美兰染料法示踪和定位乳腺癌前哨淋巴结（SLN）的可行性和预测乳腺癌腋窝淋巴结（ALN）转移的准确性。方法对66例临床0-Ⅱ期乳腺癌患者在乳晕下及肿瘤周围皮下注射国产蓝色染料亚甲蓝示踪和定位前哨淋巴结,行前哨淋巴结活检并腋窝淋巴结清扫,对全部的前哨淋巴结和腋窝淋巴结行病理检查并分析结果。结果66例中成功检出前哨淋巴结62例,检出率93．9％（62／66）;SLN对ALN状况预测的灵敏度为85．5％（53／62）;准确性为91．9％（57／62）;假阴性率为12．2％（5／41）;假阳性率为0（0／41）。结论使用国产染料亚甲蓝示踪和定位乳腺癌前哨淋巴结是可行的,在乳腺癌中有良好的成功率,能较准确地预测腋窝淋巴结的情况。     

VEGF-C介导的乳腺癌肿瘤淋巴管生成及定位

目的：探讨血管内皮生长因子C（vascular endothelial growth factor C，VEGF-C）介导的乳腺癌肿瘤淋巴管生成及定位。方法：分子生物学原位杂交方法检测VEGF-C mRNA基因在89例原发性乳腺癌组织中的表达；免疫组化SP法对乳腺癌肿瘤淋巴管进行血管内皮生长因子受体3（vascular endothelial growth factor receptor-3，VEG-FR-3）标记。结果：在89例原发性乳腺癌组织中，49例表达VEGF-C mRNA，表达率为55．06％。VEGF-C mRNA的表达与乳腺癌淋巴管密度（lymphatic vessel density，LVD）和腋淋巴结转移呈正相关；与VEGF-CmRNA阴性组相比，VEGF-C mRNA阳性组的肿瘤淋巴管密度大、腋淋巴结转移率高（均P〈0．05）；所有病例都有不同程度的淋巴管生成，但以肿瘤间质组织中淋巴管生成为主，癌巢中未见到明显的成形淋巴管。肿瘤淋巴管密度与乳腺癌临床分期和腋淋巴结转移呈正相关，临床分期越晚，肿瘤淋巴管密度越高（P〈0．05）；腋淋巴结转移组的肿瘤淋巴管密度比无淋巴结转移组高（P〈0．05）。结论：原发性乳腺癌组织VEGF-C mRNA的表达与乳腺癌肿瘤淋巴管生成、腋淋巴结转移呈正相关；VEGF-C介导的乳腺癌肿瘤淋巴管生成主要发生在肿瘤间质组织中。     

超声造影与MRI对乳腺癌患者腋窝淋巴结诊断价值

目的比较超声造影和MRI对乳腺癌患者腋窝淋巴结诊断价值。方法回顾分析常规超声诊断为乳腺癌患者的腋窝淋巴结超声造影与MRI影像学资料,以临床病理结果为"金标准",比较两种方法诊断腋窝淋巴结转移的价值。结果病理结果显示97枚腋窝淋巴结中,淋巴结转移69枚,淋巴结无转移28枚;超声造影诊断乳腺癌患者腋窝淋巴结转移的灵敏度、特异度、准确率分别为79.71%、96.43%、84.54%;MRI诊断乳腺癌患者腋窝淋巴结转移的灵敏度、特异度、准确率分别为88.41%、92.86%、89.69%;超声造影结果显示腋窝淋巴结转移组的SImax-SImin显著高于无转移组(P<0.05),MRI结果显示腋窝淋巴结转移组的淋巴结短径、长径及皮质厚度均高于无转移组(P<0.05)。结论两种方法均可有效诊断乳腺癌患者腋窝淋巴结转移,可以依据检查方法的特点为患者选择合适的诊断方法。     

Contribution of minute axillary lymph nodes to accurate staging for patients with breast cancer

Background Axillary lymph node metastasis is a very important metastatic pathway in breast cancer and its accurate detection is important for staging tumour and guiding therapy. However, neither the accuracy of routine detection of lymph node in surgical specimens nor the significance of minute lymph node with metastases in breast cancer is clear. A modified method for conveniently detecting minute lymph node in specimens of axillary dissections in patients with breast cancer was used to analyze their influence on staging breast cancer. Methods Lymph nodes in fresh, unfixed, specimens of axillary dissections from 127 cases of breast cancer were detected routinely. Then the axillary fatty tissues were cut into 1 cm thick pieces, soaked in Carnoy’s solution for 6 to 12 hours, taken out and put on a glass plate. Minute lymph nodes were detected by light of bottom lamp and examined by routine pathology. Results Lymph nodes (n= 2483, 19.6±8.0 per case) were found by routine method. A further 879 lymph nodes up to 6 mm (781 &lt; 3 mm, 6.9±5.3 per case, increasing mean to 26.5±9.7) were found from the axillary tissues after soaking in Carnoy’s solution. By detection of minute lymph nodes, the stages of lymph node metastasis in 7 cases were changed from pathological node (pN) stage pN(0) to pN(1) in 4 cases, from pN(1) to pN(2) in 2 and from pN(2) to pN(3) in 1. Conclusions The accurate staging of axillary lymph node metastasis can be obtained routinely with number of axillary lymph nodes in most cases of breast cancer. To avoid neglecting minute lymph nodes with metastases, small axillary nodes should be searched carefully in the cases of earlier breast cancer with no swollen axillary nodes. Treatment with Carnoy’s solution can expediently detect minute axillary nodes and improve the accurate staging of lymph nodes in breast cancer.     

兔子宫内膜移植肿瘤模型的建立及其转移性淋巴结的MR观察

目的 建立子宫内膜VX2肿瘤模型并行MR观察.方法 采用子宫内膜分离组织包埋法在12只兔子宫内膜制备VX2肿瘤模型,3周后行MR检查,观察肿瘤及其转移性腹膜后淋巴结,并与正常组兔腹膜后淋巴结在大小和信号强度方面进行比较.结果 肿瘤原位移植成功率为100%,3周时肿瘤浸润子宫浆膜并发生腹膜后淋巴结转移;MR检查显示肿瘤转移性淋巴结大于正常组淋巴结,但两者在信号强度方面无显著差异.结论 此模型移植成功率高,其转移模式与人子宫内膜肿瘤转移方式类似,为研究新型MR淋巴造影对比剂提供了较理想的大动物模型.     

超顺磁性氧化铁增强MRI检测转移性淋巴结的实验研究

目的探讨超顺磁性氧化铁粒子(SPIO)增强MRI检测转移性淋巴结的价值。方法取新西兰兔12只,6只于后腿肌肉接种VX2癌细胞,用于建立肿瘤转移性淋巴结模型;6只作为正常对照组。皮下间隙注射SPIO(每肢10 μmol Fe),在注射前和注射后12 h行MRI扫描,序列包括自旋回波(SE )T1WI、SE T2WI和梯度回波(GRE)T2WI,并与病理结果对照。结果平扫时,正常淋巴结和VX2转移淋巴结在三个序列图像上均表现出相似的信号特点。在增强SE T1WI 上,两组淋巴结的信号强度均未见变化;在增强SE T2WI上,正常淋巴结的信号强度不均匀降低,VX2转移组淋巴结的信号强度未见明显变化;在增强GRE T2WI上,正常淋巴结的信号强度明显地均匀降低,而VX2转移组有4个淋巴结信号强度未见降低,2个淋巴结不均匀降低。结论SPIO增强MR成像可用于检测转移性淋巴结。     

脂肪溶解液在乳腺癌腋淋巴结清扫术中的应用

目的:探讨脂肪溶解液在乳腺癌腋淋巴结清扫术中应用的可行性。方法:对38例术前扪及腋淋巴结肿大的乳腺癌患者(观察组)行改良根治术,腋窝注射脂肪溶解液及脂肪抽吸后进行淋巴结清扫术,术中保留肋间臂神经、胸长神经及胸背神经。对照组20例采用传统方法清扫腋窝淋巴结。结果:观察组术中出血少,平均每例取出淋巴结15个,所有患者术后均无明显并发症,术后平均随访6个月,均无腋窝肿瘤复发、肩关节活动障碍、上肢水肿及麻痹等情况。观察组术后发生皮下积液及上肢疼痛、上肢水肿等低于对照组(P0.01)。结论:采用脂肪溶解液及脂肪抽吸方法的腋淋巴结清扫术,具有操作简单、省时及淋巴结清扫较彻底、神经血管损伤少等优势。     

活性炭-表阿霉素混悬液对乳腺癌腋窝淋巴结转移的治疗作用

目的评价活性炭微粒-表阿霉素(Epi-CH)混悬液对乳腺癌腋窝淋巴结清扫和转移灶化疗的改进作用。方法60例II-III期乳腺癌病人随机分为两组,治疗组40例术前72h于瘤床或肿瘤周围腺体注射Epi-CH混悬液10mg,对照组20例注射表阿霉素水溶液10mg,术后清点腋窝淋巴结总数和黑染淋巴结数并计算腋窝淋巴结清除率。用高效液相色谱法检测治疗组黑染和未黑染淋巴结中表阿霉素的含量。光镜观察淋巴结组织变性坏死改变。结果治疗组平均每例清除淋巴结比对照组多4.04个(P<0.01)。治疗组中腋窝淋巴结的黑染率为86.9%(565/650);直径≤1.0cm淋巴结黑染率明显高于直径﹥1.0cm淋巴结黑染率(P<0.01);黑染淋巴结癌转移率与未黑染淋巴结转移率无显著性差异(P>0.05)。治疗组黑染淋巴结中表阿霉素的含量是未黑染淋巴结含量的14.3倍(P<0.01)。黑染淋巴结内癌细胞有明显的变性坏死改变。结论Epi-CH混悬液能增加手术清除的腋淋巴结数目,显著增加并维持表阿霉素在局部淋巴结中的高浓度。     

448例浸润性乳腺癌患者腋窝淋巴结转移规律的回顾性分析

目的探讨浸润性乳腺癌腋窝淋巴结转移规律。方法回顾性分析448例病理证实为浸润性乳腺癌患者的资料。结果 448例患者中腋窝淋巴结转移255例(56.9%),无转移193例(43.1%);对年龄、雌激素受体(ER)、孕激素受体(PR)、HER-2、分子亚型、肿块大小、肿块部位与腋窝淋巴结转移关系进行分析,P值分别为0.858、0.822、0.660、0.844、0.972、0.000、0.001。结论腋窝淋巴结的转移与肿块大小、肿块部位相关(P<0.05),而与年龄、ER、PR、HER-2、分子亚型无统计学意义上的相关性。