荷VX2移植性乳腺癌兔区域淋巴组织靶向化疗的实验研究

目的:研究对荷VX2乳腺癌兔实施区域淋巴组织靶向化疗后的局部淋巴结药物浓度及治疗效果。方法:40只雌性新西兰兔随机分为A、B、C、D4组,每组10只,VX2肿瘤组织块悬液注射法建立乳腺癌模型,腋淋巴结最大径达到5mm时开始治疗。A、B组分别给予肿瘤周围皮下注射卡铂活性碳混悬液(carboplatinactivatedcarbonsuspension,CPCH)或卡铂水溶液(carboplatinsolution,CPSol);C、D组分别经耳缘静脉注射CPSol或生理盐水。A、B、C组每次治疗药物剂量5mg/kg,每48h重复给药1次,治疗3次,48h后切除肿瘤、腋窝淋巴结及所有发现的远处转移灶,测量治疗前后肿瘤及淋巴结体积变化,原子吸收光谱法(atomicabsorptionspectrometry,AAS)测定卡铂浓度,常规病理切片观察肿瘤及转移灶坏死情况,RTPCR检测肿瘤组织增殖细胞核抗原(PCNA)。结果:与静脉或局部注射CPSol相比,局部注射CPCH可明显增加淋巴结内的药物浓度,并对淋巴结癌转移灶表现出更为显著的疗效,淋巴结增长减缓,淋巴结转移癌细胞大量死亡,PCNA表达降低。静脉注射CPSol可有效抑制乳腺或远处转移灶内的癌细胞增殖,而局部注射CPSol或CPCH无此效果。结论:区域淋巴组织靶向化疗对乳腺癌淋巴途径转移是一种有效的治疗手段,可辅助用于全身治疗。     

乳腺癌局部注射卡铂-活性碳后的淋巴趋向性研究

目的:研究乳腺癌原发灶周围皮下注射卡铂-活性碳混悬液(CP-CH)后是否提高腋窝淋巴结中的药物浓度。方法:32例乳腺癌患者随机分为两组,每组16例。在乳腺癌原发灶周围皮下,一组患者注射CP-CH,另一组患者注射卡铂水溶液(CP-Sol)作为对照。给药后1、12、24、72小时分别行乳腺癌改良根治术(每组4例),术中常规行腋窝淋巴结清扫,原子吸收光谱法测定淋巴结内卡铂浓度。结果:CP-CH组给药后1、12、24、72小时淋巴结中卡铂浓度分别为11.23±5.66μg/g、26.40±11.18μg/g、18.72±7.14μg/g、15.44±6.92μg/g,CP-Sol组在相应各时间点则分别为0.24±0.06μg/g、0.13±0.08μg/g、0.12±0.04μg/g,第72小时淋巴结内未检测出卡铂。两组间有统计学显著差异(P<0.01)。结论:乳腺癌局部注射CP-CH后有良好的淋巴趋向性,可显著提高腋窝淋巴结中的药物浓度。     

大肠癌腹腔淋巴化疗的临床研究

目的：探讨腹腔化疗时联合应用善得定对腹腔淋巴化疗的临床效果,为具有高淋巴转移倾向的大肠癌患者开展腹腔淋巴提供实验依据。方法：对２３例大肠癌患者行术前卡铂腹腔化疗１０例,卡铂加善得定诱导腹腔淋巴化疗１３例,于术中不同时段内分别取门静脉血和癌灶旁淋巴结标本,用原子吸收光谱法测定样本铁浓度。结果：两组间静脉血铂浓度无差异;１～２小时时两组间淋巴结样本铂浓度相比无差异（Ｐ〉０．０５）,３小时时实验组淋巴结     

胃癌腹腔淋巴化疗的临床研究

目的：探讨胃癌患者行腹腔化疗时联合应用善得定诱导腹腔淋巴化疗临床应用。方法：对34例胃癌患者术中行卡铂腹腔化疗19例(对照组），卡铂＋善得定诱导腹腔淋巴化疗15例（实验组），手术中不同时段内分别取门静脉血和癌旁淋巴结标本，用原子吸收光谱法测定样本的铂浓度。结果：两组间门静脉血铂浓度无明显变化；1－2小时两组间淋巴结样本铂浓度相比无差异（P＞0．05），3小时实验组淋巴结样本铂浓度明显高于对照组（P＜0．05）。结论：行腹腔化疗时联合应用善得定可促进化疗药物增量进入腹腔区域淋巴系统，诱导腹腔淋巴化疗。     

术前淋巴化疗对乳腺癌复发转移的影响及其机制

背景与目的:有报道认为淋巴化疗可以增加消化道肿瘤引流区域淋巴结中抗癌药物的浓度,改善预后,关于乳腺癌淋巴化疗的研究尚少见报道。本研究探讨术前淋巴化疗对乳腺癌复发转移的影响及其作用机制。方法:将60例Ⅱ～Ⅲ期乳腺癌患者随机分为两组,淋巴化疗组40例,对照组20例。在改良根治术前72h,淋巴化疗组于肿瘤周围或瘤床注射表阿霉素-活性炭混悬液10mg;对照组注射表阿霉素水溶液10mg,注射部位和方法同淋巴化疗组。用末端转移酶标记法检测腋窝转移淋巴结癌细胞凋亡指数(apoptoticindex,AI);用免疫组化SP法检测Fas/Fas-L蛋白的表达。观察两组患者局部和全身反应,比较复发转移率。结果:淋巴化疗组转移癌细胞AI平均为(9.5±2.7)%,对照组平均(3.8±1.4)%,前者明显高于后者(P﹤0.01);淋巴化疗组Fas蛋白表达比对照组明显上升(P﹤0.05),而Fas-L蛋白表达无明显改变(P﹥0.05)。对照组中有5例患者出现注射部位皮肤红肿发热,两组均无与化疗有关的局部和全身不良反应。淋巴化疗组患者的2年复发转移率为10.34%,低于对照组的38.46%(P﹤0.05)。结论:乳腺癌术前应用活性炭-表阿霉素混悬液淋巴化疗,可能会降低乳腺癌的复发转移率,其作用可能是通过上调Fas蛋白表达、诱导腋窝转移淋巴结癌细胞凋亡实现的。     

区域淋巴组织靶向化疗诱导兔乳腺移植性鳞癌模型淋巴结转移癌细胞凋亡

目的：研究区域淋巴组织靶向化疗是否能有效诱导兔乳腺移植性鳞癌模型腋窝淋巴结转移癌细胞凋亡，并与常规静脉化疗作比较。方法：30只乳腺种植VX2肿瘤的新西兰兔随机分为3组，每组10只。腋淋巴结最大直径达到5mm时开始治疗。淋巴化疗组：肿瘤周围皮下注射多柔比星脂质体(LADR)；静脉化疗组：经耳缘静脉注射多柔比星水溶剂(FADR)；对照组：皮下注射生理盐水。治疗组单次给药剂量均为1mg／kg，每48小时重复给药1次，共给药3次。第3次治疗后48小时切除腋淋巴结，测量治疗前后淋巴结体积，TUNEL检测转移灶癌细胞凋亡指数(AI)，ANOVA-LSD多重比较分析组间差异。结果：与对照组相比，治疗组均出现淋巴结增长减慢，淋巴化疗组的抑制作用又强于静脉化疗组(P=0．002)。淋巴化疗、静脉化疗组均可见明显的转移癌细胞凋亡，平均AI分别为21．73％、15．31％，与对照组(5．16％)相比均有显著差异(P=0．000)，淋巴化疗组又显著高于静脉化疔组(P=0．000)。结论：与静脉化疗相比，区域淋巴组织靶向化疗能更加有效地诱导乳腺癌淋巴转移灶的肿瘤细胞凋亡。     

新辅助化疗对腋窝淋巴结数量影响随机对照临床研究

目的：探讨新辅助化疗（neoadjuvant chemotherapy,NAC）对乳腺癌患者腋窝淋巴结数量的影响。方法：2010—03—02—2012—06—30临沂市人民医院乳腺外科收治82例临床Ⅱ～Ⅲ期乳腺癌患者,随机数字表法分为化疗组40例和手术组42例,化疗组以蒽环类CEF或EC方案行3～4个周期NAC,手术组直接接受乳腺癌改良根治术,比较两组患者的腋窝淋巴结数量。结果：40例经NAC的乳腺癌患者中,目标病灶完全缓解（CR）6例,部分缓解（PR）19例,病情稳定（SD）15例,无患者出现疾病进展（PD）。腋窝淋巴结清除以后,化疗组平均检出淋巴结总数为16．7枚（8～28枚）,手术组为20．4枚（12～37枚）;平均阳性淋巴结数化疗组为2．1枚（0～13枚）,手术组为6．5枚（0～20枚）,两组间差异均有统计学意义,P值均〈0．001。结论：乳腺癌患者接受NAC以后,进行腋窝淋巴结清除时,不仅阳性淋巴结减少,得到的淋巴结总数也减少。     

新辅助化疗对大肠癌患者淋巴结转移的影响

目的研究奥沙利铂联合亚叶酸钙及5-Fu新辅助化疗对大肠癌患者淋巴结转移的影响。方法将136例无远处转移的大肠癌患者随机分成A、B两组,A组行新辅助化疗两个疗程后手术治疗,B组直接手术治疗。分析两组患者出现淋巴结转移的人数、淋巴结转移总数目及两组分期。结果A组21例发生淋巴结转移(30.9%),B组33例发生淋巴结转移(48.5%,P<0.05)。A组共取淋巴结1091枚,发现106枚有癌转移(9.9%);B组共取淋巴结1106枚,发现143枚有癌转移(12.9%,P<0.05)。结论奥沙利铂联合亚叶酸钙及5-Fu新辅助化疗可减少大肠癌患者的淋巴结转移。     

术前腹腔和静脉卡铂化疗肿瘤组织聚积浓度的比较研究

目的：探讨不同给药途径卡铂在肿瘤组织内药物浓度的聚积性。方法：采用高效液相色谱法对２０例可切除进行期胃癌进行腹腔和静脉卡铂术前化疗药代动力学研究。卡铂３００ｍｇ／ｍ２加生理盐水７５０ｍｌ分别静脉、腹腔１次注射，给药后２４０～２７０ｍｉｎ手术取癌组织、癌旁正常组织、腹膜、大网膜、阴性淋巴结，测定总铂浓度。结果：腹腔给药组各组织浓度明显高于静脉给药组（Ｐ＜０．０１），其中腹膜浓度最高，其次为癌组织、大网膜、癌旁正常组织及阴性淋巴结，分别超出静脉给药的３．６、２．５、３．０、２．８、１．９倍。癌组织含量高于正常组织。结论：术前卡铂腹腔化疗大大提高腹膜、肿瘤组织内浓度，延长药物作用时间，使对药物敏感癌细胞得到控制。对杀灭腹腔亚临床病灶，控制医源性转移，提高治愈性手术切除率颇有意义     

超选择子宫动脉与外周静脉灌注化疗宫颈癌组织内铂浓度的研究

目的:对比卡铂超选择子宫动脉与外周静脉灌注化疗子宫颈癌组织内的药物浓度。方法:选择经病理活组织证实为宫颈癌、且癌灶较大易于取材的患者13例,随机分为超选择子宫动脉灌注化疗组(A组)和外周静脉灌注化疗组(B组),以卡铂300mg/m2,一次性给药。在灌注后0min、10min、20min分别钳取宫颈癌组织,用原子吸收光谱法测定其标本内铂离子浓度。结果:(1)峰值及曲线形态:A组癌组织铂离子浓度的高峰值出现在化疗结束后即刻,且随时间的延长而快速下降,呈一下降曲线;B组峰值出现在化疗后10分钟,随时间的延长呈一弓背向上的下降曲线。前者的峰值是后者的2.79倍,差异有统计学意义(P<0.05)。(2)灌注化疗结束后即刻,A组宫颈癌组织内铂离子浓度是B组的3.75倍,差异有统计学意义(P<0.05)。(3)A组癌组织内铂离子药时曲线下面积(AUC0～20min)是B组的2.10倍,差异有显著意义(P<0.05)。结论:无论癌组织内铂离子峰浓度还是AUC0～20min,超选择子宫动脉灌注化疗组均较外周静脉组明显增高,为评价动脉化疗疗效提供了基础理论依据及临床药代动力学参数。     

Drug concentrations in axillary lymph nodes after lymphatic chemotherapy on patients with breast cancer

Background  

Lymph node status is one of the decisive prognostic factors in breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising therapy for the treatment of malignancies with a high tendency to disseminate lymphatically. The present study determined the drug concentrations in axillary lymph nodes after lymphatic chemotherapy (LC) in patients with breast cancer and compared the results with those receiving intravenous chemotherapy (VC) to investigate whether LC could improve the accumulation of anticancer drug in regional lymph nodes.     

T1-T2 breast cancer with four or more positive axillary lymph nodes: adjuvant locoregional radiotherapy with high-dose or standard-dose chemotherapy. Results of an observational study

AIM AND BACKGROUND: The aim of this study was to investigate the efficacy of postoperative locoregional radiotherapy in patients with T1-T2 breast cancer and four or more positive axillary lymph nodes submitted to mastectomy or breast-conserving surgery followed by standard-dose or high-dose adjuvant chemotherapy. The incidence of locoregional relapses and the survival correlated with the number of positive nodes were recorded for each treatment arm. PATIENTS AND METHODS: From August 1992 to August 1999 86 breast cancer patients (median age, 54 years, T1-T2, N+ > or = 4) submitted to surgery were treated. Sixty-three patients received standard-dose chemotherapy while 23 patients with 10 or more positive nodes received high-dose chemotherapy. After four courses of standard-dose anthracycline-based chemotherapy peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (10-16 microg/kg/day/sc). High-dose chemotherapy consisted of etoposide 1000 mg/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2. Hormone receptor-positive patients underwent hormone therapy. Following chemotherapy all 86 patients were given conventional radiotherapy to the breast or the chest wall and the supraclavicular fossa. The high-dose subgroup received radiotherapy to the internal mammary nodes +/- axilla. RESULTS: The median follow-up from the start of radiotherapy was 36.5 months. Locoregional relapses occurred in nine patients (10.4%); in four of them they were isolated (4.6%). Local relapses were four (4.6%) and regional relapses six (6.9%). Twenty-five patients (29%) had distant metastases. The five-year and eight-year overall actuarial survival rates were 82.6% +/- 4.8 and 60.1% +/- 8.8, respectively. No statistical differences were found when the number of positive nodes or the type of treatment of N+ 10 patients was included in the analysis. CONCLUSIONS: Breast cancer patients with four or more positive axillary lymph nodes are at high risk of developing locoregional and distant relapses. The results reported here demonstrate the efficacy of radiotherapy in the reduction of locoregional failure; no differences in survival and locoregional control in relation to treatment arm and number of positive nodes were found.     

Is sentinel lymph node biopsy reliable and indicated after preoperative chemotherapy in patients with breast carcinoma?

BACKGROUND: Many studies support the concept and accuracy of sentinel lymph node biopsy (SNB) for staging patients with breast carcinoma, which can be performed with low morbidity in lymph node negative patients. Preoperative chemotherapy (PC) plays an important role in the treatment of patients with operable breast carcinoma and is another approach with which to reduce radical surgery in patients with more advanced disease. It is of interest whether the sentinel lymph node accurately represents the axillary status after PC and, thus, whether the sentinel node concept can be applied to both groups. METHODS: Thirty-three patients underwent SNB after chemotherapy and prior to axillary lymph node dissection. RESULTS: The average greatest tumor dimension before chemotherapy (33 mm +/- 2 mm) was significantly larger (P = 0.000) than after therapy (20 mm +/- 3 mm). Histopathologic complete remission was seen in only three patients. One or two sentinel lymph nodes (average, 1.7 lymph nodes) were identified with certainty in 29 of 33 procedures and accurately predicted axillary lymph node status in all of these patients. Breast-conserving surgery was possible in 21 patients (64%), and axillary lymph nodes were involved in 22 patients (67%). CONCLUSIONS: Even after patients undergo PC, SNB seems to be a reliable method for accurate staging of the axilla in those more advanced breast carcinoma. Thus, axillary dissection may be avoided in certain patients. Lymph node involvement seems to be likely in women with suspicious axillary findings before chemotherapy who have no visible sentinel lymph nodes on preoperative lymphosintigraphy and in patients without recurrent tumors. Further investigation of the SNB concept in this patient group should be evaluated in larger studies.     

Extranodal extension of axillary metastasis of invasive breast carcinoma as a possible predictor for the total number of positive lymph nodes

INTRODUCTION: By the implementation of the sentinel node procedure in the treatment of breast carcinoma routine axillary lymph node, dissection can be abandoned in patients with a tumour-negative sentinel node. When the sentinel node is positive there are two options; an axillary dissection or radiotherapy of the axilla. In the latter case one is not informed about the total number of positive lymph nodes which can be of importance for the choice of adjuvant chemotherapy. In this paper we analyse whether it is possible to use histological parameters of a lymph-node metastasis to predict the number of tumour-cell-containing nodes. METHODS: Four hundred and ninety-eight patients treated for invasive breast cancer at our department from 1991 to 1996 were investigated to see whether extranodal extension of axillary metastases had a significant predictive value for the number of positive lymph nodes. Extranodal extension was scored as: no extranodal extension (NEE) and extranodal extension (EE); the latter was subdivided in minimal extranodal extension (MEE) or extensive extranodal extension (EEE). RESULTS: Of 498 patients, 230 patients had axillary involvement. NEE was seen in 83 (36.1%) patients and 147 (63.9%) had EE. Subdivision of this latter group revealed 77 patients with MEE (52%), 65 patients with EEE (45%) and five patients not further specified (3%). The number of positive nodes for the EE-group (6.9+/-0.5) was significant higher compared with the NEE-group (2.1+/-0.2) (P<0.001). The number of positive nodes was also significantly higher for the EEE-group compared to the MEE-group, 10.6+/-0.8 vs 4.0+/-0.4 (P<0.001). The predictive value for > or =4 positive axillary lymph nodes was 84.6% for EEE, 58.5% for EE and only 14.5% for NEE. These differences were significant (P<0.001). CONCLUSIONS: The presence of extranodal extension in axillary lymph-node metastases can be a good predictor for the expected number of positive nodes. This histological parameter could be of value to determine the kind of adjuvant chemotherapy after a positive sentinel-node biopsy with only radiotherapy of the axilla and no further axillary lymph-node dissection.     

Accuracy of fine-needle aspiration cytology of axillary lymph nodes in breast cancer patients: a study of 115 cases with cytologic-histologic correlation

BACKGROUND: Fine-needle aspiration (FNA) cytology of axillary lymph nodes is a simple, minimally invasive technique that can be used to improve preoperative determination of the status of the axillary lymph nodes in patients with breast cancer, thereby serving as a tool with which to triage patients for sentinel versus full lymph node dissection procedures. The aim of the current study was to determine the sensitivity and specificity of FNA cytology to detect metastatic breast carcinoma in axillary lymph nodes. METHODS: A total of 115 FNAs of axillary lymph nodes of breast cancer patients with histologic follow-up (subsequent sentinel or full lymph node dissection) were included in the current study. The specificity and sensitivity, as well as the positive and negative predictive values, were calculated. RESULTS: The positive and negative predictive values of FNA cytology of axillary lymph nodes for metastatic breast carcinoma were 1.00 and 0.60, respectively. The overall sensitivity of axillary lymph node FNA in all the cases studied was 65% and the specificity was 100%. The sensitivity of FNA was lower in the sentinel lymph node group than in the full lymph node dissection group (16% vs 88%, respectively), which was believed to be attributable to the small size of the metastatic foci in the sentinel lymph node group (median, 0.25 cm). All false-negative FNAs, with the exception of 1 case, were believed to be the result of sampling error. There was no 'true' false-positive FNA case in the current study. CONCLUSIONS: FNA of axillary lymph nodes is a sensitive and very specific method with which to detect metastasis in breast cancer patients. Because of its excellent positive predictive value, full axillary lymph node dissection can be planned safely instead of a sentinel lymph node dissection when a preoperative positive FNA result is rendered. .     

Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes?

The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer.     

Chemotherapy targeting regional lymphatic tissues to treat rabbits bearing VX2 tumor in the mammary glands

Lymph node status is one of the decisive prognostic factors in breast cancer. Chemotherapy targeting regional lymphatic tissues has emerged as a promising approach for the treatment of malignancies with high tendency to disseminate lymphatically. In this study, rabbits bearing well-developed VX2 tumors in the mammary gland received carboplatin-activated carbon suspension (CP-CH) administered subcutaneously (s.c.), carboplatin solution (CP-Sol) s.c., CP-Sol intravenously (i.v.), or a sham therapy, respectively, 6 weeks after tumor implantation. The platinum concentrations in breast tumors, axillary lymph nodes and distant metastases were determined by Zeeman atomic absorption spectrometry (AAS). Therapeutic effects were assessed in terms of tumor and node volume ratio, cell proliferation and necrosis. Compared to CP-CH or CP-Sol s.c., CP-Sol i.v. exhibited more marked cytotoxic efficacy on breast tumor and distant metastases. In contrast, CP-CH s.c. produced much higher drug concentrations and more evident antitumor activities in axillary nodes, as demonstrated by the inhibited node growth, declined mRNA level of proliferating cell nuclear antigen (PCNA), and more extensive tumor necrosis. Based on these data, we recommend lymphatic chemotherapy to be used as an effective component of the approach to the systemic treatment on breast cancer patients with positive lymph nodes.     

Accuracy of Methylene Blue Test as Single Technique for Sentinel Lymph Node Biopsy in Early Stages Breast Cancer

Aim: Sentinel Lymph Node Biopsy (SLNB) establishes as a gold standard for diagnostic lymph node involvement in early breast cancer. Most of the developed country does not have radiotracer and nuclear medicine facilities. Unless in Indonesia there is Methylene Blue as an alternative agent for SLNB. This study measure accuracy of sentinel lymph node biopsy as a single technique using the Methylene Blue test. Methods: This cross-sectional study enrolled 60 female patients with breast cancer stage I-II. We performed SNB using 2-5 cc of 1% Methylene-blue dye (MBD) injected to periareolar tissue and proceeded with axillary lymph nodes dissection (ALND). The histopathology results of sentinel nodes (SNs) and axillary lymph nodes (ALNs) analyze for diagnostic value assessments. Results: The identification rate of SN was 97.62 %, and the median number of identified SNs was 4 (2-7). Sentinel node metastasis was found in (19/60) % cases and % of them were macrometastases. The sensitivity and specificity of MBD were 91.67% and 96.67% respectively. The negative predictive value (NPV) of SNs to predict axillary metastasis was 96.67% (95% CI, 81-99%). Conclusion: Injection of 1% MBD as a single technique in breast cancer SNB has a favorable identification rate and predictive value.     

前哨淋巴结活检在早期乳腺癌患者腋窝管理中的研究进展

传统的观点认为腋窝淋巴结清扫(axillary lymph node dissection,ALND)是前哨淋巴结(sentinellymph node,SLN)阳性乳腺癌患者的标准治疗方法,而ALND容易引起上肢水肿、功能障碍等术后并发症,影响患者生活质量.近几年研究显示,对于SLN阳性的早期乳腺癌,并非所有患者都需...