1、先进治疗理念引导治疗进步,军事医学科学院附属307医院全军肿瘤中心尉承泽,4P模式预测（Prediction）预防（Prevention）个性化（Personalization）参与（Participation）,TIDEST模式靶点（Targeted）整合（Integrated）以数据为基础（Data-based）循证为基础（Evidence-based）系统医学（SystemsMedicine）转化医学（TranslationalMedicine）,“精准医学”概念：对4P模式和TIDEST模式的整合接地气！,治疗理念,基于对疾病的认知治疗手段国情时效性，阶段性整合医疗资源-患者利益最大化
2、,治疗理念,基于对疾病的认知深入治疗手段-丰富国情发展时效性，阶段性患者利益最大化,不断优化的治疗理念引导治疗方式的进步,乳腺癌外科发展史乳腺癌根治术 1894年 Halsted乳腺癌扩大根治术 1949年 Urban 1951年 Margottini乳腺癌改良根治术 1948年 Patey and Dyson 1963年 Auchincloss保留乳腺手术加放疗 1927年 Hirsch 保留乳腺的乳腺癌根治术 1954年 Muslakallio哨兵淋巴结活检术 1993年 Krag,基于病理解剖学的手术阶段,Rudolf Virchow,最大限度的可耐受切除,认为乳腺癌属于局部病变，区域淋
3、巴结是癌细胞通过的屏障。手术包括肿瘤及乳腺,胸大小肌和腋窝淋巴结的广泛切除。,Halsted乳腺癌根治术,1918年，Stibbe通过尸体解剖，描述了内乳淋巴结的分布。20-40年代，使人们认识到乳腺癌除了腋窝淋巴结转移途径外，内乳淋巴结同样也是乳腺癌淋巴结转移的第一站。锁骨上、纵隔淋巴结为第二站。经典的乳腺癌根治术是否遗漏了重要的淋巴引流区域-内乳淋巴结,乳腺癌扩大根治术,Margotini（1949年） 根治术+胸膜外内乳淋巴结切除Urban（1951年） 根治术+胸膜内内乳淋巴结切除,乳腺癌超根治术,Anderssen 根治术+内乳淋巴切除Dahl-Iversen +锁骨上淋巴结切除,（
4、1954年）,乳腺癌超根治术,Wangensteen（1956年） 根治术+内乳淋巴切除 +锁骨上淋巴结切除 +纵隔淋巴结切除共64例，死亡率12.5%。,越大越好？,根治术基础上的扩大（超）根治术疗效没有提高并发症提高死亡率提高,肢体及功能保留,Patey and Dyson (1948年）保留胸大肌的改良根治术。40例随访时间短,Auchincloss （1963年）保留胸大、小肌的改良根治术,根据肿瘤生物学特性研究手术方案,Bernard Fisher,随着生物学、免疫学研究的深入Fisher提出：乳腺癌是全身性疾病，区域淋巴结虽然具有重要的生物学免疫作用，但不是癌细胞的有效屏障，血流转
5、移更具临床意义。,改良根治术,国际协作的多中心、前瞻性随机试验比较了乳腺癌根治术与改良根治术随访10-15年生存率无统计学差别；形体效果，上肢功能，改良根治术优于根治术；,美国医师协会 Halsted1950年 75%1970年 60%1972年 48%1977年 21%1981年 3%,改良根治术1950年 5%,1972年 28%,1981年 72%,保留乳腺手术加放疗 1927年 Hirsch 保留乳腺的乳腺癌根治术 1954年 Muslakallio 象限切除 区段切除 + 腋窝淋巴结清扫 局部切除,意大利米兰国立癌症研究院NSABP B-06EORTC-10801比较保留乳腺+放疗与
6、改良根治术的结果,1995年EBCTC 保留乳腺+放疗与改良根治术的结果Meta分析：10年死亡率均为22.9%；10年局部复发率5.9%/6.2%；,我院1986年开始保留乳腺+放疗治疗早期乳腺癌。新辅助化疗后保乳。,最小的有效治疗,最大限度的可耐受切除,肢体功能保留,保留乳腺+放疗治疗早期乳腺癌美国 50%新加坡 7080%日本 40%香港 30%中国 20%,保乳手术目的,良好的肿瘤局部控制效果 降低手术对患者的损伤 保持乳房的自然形态 提高生活质量,所有术式均包括同侧腋窝淋巴结清扫,出血，积液；感染；肢体感觉、运动障碍；神经，血管损伤；淋巴水肿等.,T1a 16%T1b 18%23cm
7、 30%,腋窝淋巴结转移率,Rivadenier DE, et al: J-Am-Coll-Surg. 2000 Jul: 191(1):1-8.,当腋淋巴结无转移时 腋淋巴结清扫过度治疗,腋淋巴结清扫的主要意义准确的病情分期预后判断指导治疗清除转移病灶延长生存,？,不行腋淋巴结清扫如何预测腋淋巴结状态？,哨兵淋巴结活检Sentinel lymph node, SLN,Key findings of the 1960 paper by Gould and colleagues Report of a single case of supposed benign parotid tumour w
8、ith a unique and normal-appearing node which was found to be metastatic at pathological examination Introduction of the sentinel-node concept, based on the theory that tumour invasion of the first node of the regional nodal basin could indicate the tumour status of the entire nodal basin Report of s
9、imilar survival in 28 patients with radical lymph-node dissection or sentinel lymph-node biopsy,Ernest A. Gould M.D., cancer 13:1;77-78,1960,1977，Cabanas在阴茎癌外科治疗中，开始前哨淋巴结活检。 Cancer 1977,39:456-466.,1992年，Morton将SLN应用于恶性黑色素瘤的外科治疗中，取得了成功。,Morton DL, et al: Arch Surg 1992,127:392-399.,1993年，Alex率先将SLN引
10、入了乳腺癌的外科治疗临床研究。（放射性同位素示踪剂法）,Alex C, et al: Surg Oncol 1993,2:335-340.,1994年，Giuliano生物染料法进行乳腺癌哨兵淋巴结的检测。,Giuliano AE, et,al:J Clin Oncol 1997,15:2345-2350.,哨兵淋巴结（-）,原发肿瘤,SLN,ALN,哨兵淋巴结（+）,原发肿瘤,SLN,ALN,我院自2000年始开展乳腺癌前哨淋巴结活检。,哨兵淋巴结检出方法,美蓝着色法,放射性同位素示踪法,美蓝着色联合法放射性同位素示踪,前哨淋巴结（SLN）活检的意义,如果拥有一支经验丰富的前哨淋巴结活检团队
11、且患者适合做前哨淋巴结活检，前哨淋巴结活检是腋窝淋巴结分期的首选方法, NCCN乳腺癌治疗指南,The time has come to change the algorithm for the surgical management of early breast cancer.,Arch Surg 2002,137:1131-1135.,Giuliano AE:,NSABP B32 David Krag,A Randomized, Phase III Clinical Trial To Compare Sentinel Node Resection To Conventional Axil
12、lary Dissection In Clinically Node-Negative Breast Cancer Patients,ACOSOG Z0010: A multicenter prognostic study of sentinel node (SN) and bone marrow (BM) micrometastases in women with clinical T1/T2 N0 M0 breast cancer. R. Cote, A. E. Giuliano, D. Hawes, K. V. Ballman, P. W. Whitworth, P. W. Blumen
13、cranz, D. S. Reintgen, M. Morrow, A. M. Leitch and K. Hunt,ACOSOG Z0011: A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive sentinel node. A. E. Giuliano, L. M. McCall, P. D. Beitsch, P. W. Whitworth, M. Morrow, P. W. Blumencranz, A. M.
14、 Leitch, S. Saha, K. Hunt and K. V. Ballman,哨兵淋巴结（）,腋窝淋巴结清扫,X,哨兵淋巴结（ITC, Mic）,腋窝淋巴结不清扫,哨兵淋巴结（+）,部分患者腋窝淋巴结不清扫,SENTINAACOSOG 1071新辅助化疗后SLNB NO,SLNB 优于 ALND 有 创,32 papers reporting 27 independent cohort studies pain (7.5-36%) impairment of range of motio (0.031%) oedema (0.0-14%) decreased strength (11
15、.0-19%) sensory disorders (1.0-66%),Trial Z0011 Incidence of Surgical Complications by Study Group Adverse Surgical Effect SLND + ALND SLND Alone Axillary paresthesias at 30 days 174 of 373(47%) 43 of 371( 12%) .0001 at 6 months 146 of 335(44%) 35 of 288 (12%) .0001 at 12 months 113 of 287(39%) 24 o
16、f 268 (9%) .0001,Trial Z0011 Incidence of Surgical Complications by Study Group Adverse Surgical Effect SLND + ALND SLND Alone Lymphedema (reported subjectively) at 6 months 27 of 327(8%) 19 of 33(6%) at 12 months 37 of 288(13%) 16 of 268(2%) .0001 after 12 months 52 of 272(19%) 14 of 253(6%) or=10%
17、 peaked at 1 week ALND (75%) and SLND (41%)Arm volume differences or=10% at 36 months ALND (14%) and SLND (8%) Numbness and tingling peaked at 6 months ALND (49%, 23%) and SLND (15%, 10%),J Surg Oncol. Aug 1, 2010; 102(2): 111118.,(pT1 and pT2 3 cm, cN0) 449 patients, 210 patients underwent SLN and
18、completion ALND follow-ups were 31.0 and 29.5 months lymphedema (3.5% vs. 19.1%, P 0.0001) impaired shoulder range of motion (3.5% vs. 11.3%, P 0.0001)shoulder/arm pain (8.1% vs. 21.1%, P 0.0001) numbness (10.9% vs. 37.7%, P 80%ALN(-) SLNB 有创！?,腋窝淋巴结转移率,最大可耐受切除,最小有效治疗,More minimally invasive,Ultraso
19、und-guided needle biopsy (UNB),Sonographic examination 10 - 13 Mhz linear transducer Malignant features on the US examinationround morphologyirregular cortexperipheral vascularization disappearance of the hyperchogenicity of the hilum.,European Society of Mastology (EUSOMA) : U1 and U2 when the appe
20、arance of the node was either normal or generally benign; U3 when the node was suspicious but with benign features; U4 when the node was suspicious with malignant features ;U5 when the node was probably malignant.American BI-RADS,Annals of Surgery: August 2011 - Volume 254 - Issue 2 - p 243251doi: 1
21、0.1097/SLA.0b013e31821f1564Meta-AnalysisPreoperative Ultrasound-Guided Needle Biopsy of Axillary Nodes in Invasive Breast Cancer: Meta-Analysis of Its Accuracy and Utility in Staging the AxillaHoussami, Nehmat MBBS, PhD*; Ciatto, Stefano MD; Turner, Robin M. PhD*; Cody, Hiram S. III MD; Macaskill, P
22、etra PhD*,Objective: Systematic evidence synthesis of ultrasound-guided needle biopsy (UNB) of axillary nodes in breast cancer.Summary Background Data: Women affected by invasive breast cancer undergo initial staging with sentinel node biopsy, generally progressing to axillary node dissection (AND)
23、if metastases are found. Preoperative UNB can potentially identify and triage women with node metastases directly to AND.Methods: Review and meta-analysis of studies reporting UNB accuracy: we estimated sensitivity, specificity, and PPV, using bivariate random-effects models and examined the effect
24、of covariates; we calculated UNB utility (effect on axillary surgery).Results: Thirty-one studies provided 2874 UNB data from 6166 subjects (median proportion with metastatic nodes 47.2%; IQR 39.5%, 61.2%). Modeled estimates for UNB were: sensitivity 79.6% (95% confidence intervals CI 74.184.2), spe
25、cificity 98.3% (95%CI 97.299.0), PPV 97.1% (95%CI 95.298.3); median UNB insufficiency was 4.1% (IQR0%10.9%). UNB sensitivity increased with increasing ultrasound sensitivity, and was higher in studies performing UNB for “suspicious” than for “visible” nodes. Specificity was higher in studies of cons
26、ecutive (vs. selected) subjects, in studies reporting ultrasound data, and in more recent studies. Median proportion of women triaged directly to AND (attributed to UNB) was 19.8% (IQR11.6%28.1%) or 17.7% (IQR11.6%27.1%) if restricted to clinically node-negative series. Median proportion of women wi
27、th metastatic axillary nodes potentially triaged to AND was 55.2% (IQR41.8%68.2%) and was higher (65.6%; IQR48.9%69.7%) in the subgroup of studies with median tumor size 21 mm.Conclusions: Preoperative UNB of the axilla is accurate for initial staging of women with invasive breast cancer. Meta-analy
28、sis indicates that UNB provides better utility in women with average or higher underlying risk of node metastases.,UNB B-超可疑转移LN 90%可以明确避免SLNB避免术中冰冻病理检查 二次手术,临床阴性B-超 腋窝淋巴结分期 准确吗？ B-超阴性 腋窝淋巴结转移负荷有多大?,乳腺癌腋窝淋巴结转移的超声诊断价值及临床病理相关性分析辛灵*,1 陈路增*,2张虹3刘倩1 徐玲1 王彬2李挺3段学宁1 刘荫华1,特异度为97%阳性预测率为92%阴性预测率为68.6%。,B-超阴性
29、腋窝淋巴结转移率31.4%,357例行SLNB项目 B超阴性SLN阳性 42（16.5%）SLN阴性 212合计 254,B超阴性NSLN阳性 6NSLN阴性 36,B超阴性,SLN(+) 腋窝淋巴结转移转移状态,40例(T1-2;cN0)乳腺癌SLNB与B超关系,B超与SLNB,灵敏度=A/(A+C)x100%=56/(56+6)X100%=90.3%特异度=D/(B+D) x100%=92/(14+92)x100%=86.8%阳性预测值=A/(A+B) x100%=56/(56+14)x100%=80%阴性预测值=D/(C+D)x100%=92/(92+6)x100%=93.9%,肿瘤负荷
30、,腋窝（1/24）前哨（2/2） 腋窝（3/36）前哨（1/2） 腋窝（0/18）前哨（1/1） 腋窝（0/34）前哨（0/1） 腋窝（1/25） 腋窝（1/23）,临床阴性 B-超阴性腋窝淋巴结转移负荷较小甚至低于ACOSOG-Z0011,ACOSOG-Z0011SLN(+) non-SLNs (+)in 27.3%,术后化疗 放疗,Ultrasounelastography,The highest specificity of 99.3% was achieved by findings of a cortical thickness 3 mm on B-mode and blue cor
31、tex on the elastogram.,Wojcinski S, Dupont J, Schmidt W, Cassel M, Hillemanns P (2012) Real-timeultrasound elastography in 180 axillary lymph nodes: elasticity distribution in healthy lymph nodes and prediction of breast cancer metastases. BMC Med Imaging 12:35,Sever et al Contrast-enhanced ultrasou
32、nd (CEUS) It were able to confirm a sensitivity of 89 % for SLN detection compared with radioisotope and blue dye,Sever A, Jones S, Cox K, Weeks J, Mills P, Jones P (2009) Preoperative localization of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasonography in patien
33、tswith breast cancer. Br J Surg 96:12951299Sever AR, Mills P, Jones SE et al (2011) Preoperative sentinel node identification with ultrasound using microbubbles in patients with breast cancer. AJR Am J Roentgenol 196:251256,先进的检查手段-更准确的诊断,前哨淋巴结活检早期乳腺癌腋窝分期金标准,更加微创手段 UNB,Axillry stagingbloodlessIs the image time coming?,女，乳腺癌，T1.0cm，cN0,70年代前 根治术7090年代 改良根治术OR保乳+ALND90年代后 保乳+SLNB2015 保乳+SLNB？,最小的有效治疗,最大限度的可耐受切除,肢体功能保留,我有一个梦想,做女人 好,挺,做好自己保护好自己维护应有权益,谢谢!,做好自己保护好自己维护应有权益,谢谢!,
