在乳腺癌局部精准治疗中的新进展：联合免疫治疗未来可期

乳腺癌是女性最常见的恶性肿瘤,早期乳腺癌治疗以手术为主。目前,早期乳腺癌的诊治已取得了显著进展,但仍需要创新的方法来减少创伤和改善预后。随着乳腺癌治疗手段创新性研究的深入,乳房和腋窝的非手术治疗成为早期乳腺癌治疗的研究热点。微波消融作为一种微创的精准局部治疗方式,具有消融迅速、操作方式简易、术后并发症较少等特点,目前已尝试用于治疗早期乳腺癌,获得了较好的临床效果。此外,有研究报道,早期乳腺癌经微波消融可调节肿瘤免疫微环境,激发体内抗原特异性的抗肿瘤免疫反应。该免疫效应可能与微波消融后肿瘤抗原的大量释放有关。乳腺癌单用免疫治疗效果差,有研究者提出通过联合免疫治疗增强消融免疫效应的方案,但其具体疗效仍需要更多的临床数据支持。随着对于微波消融引起体内免疫效应的研究深入,微波治疗联合免疫检查点抑制剂疗法有望成为全新的精准治疗策略和理念。本文对微波消融在乳腺癌局部精准治疗中的应用研究新进展及未来发展方向进行总结。     

精准医学时代的乳腺癌个体化治疗选择

人类基因组计划以及肿瘤基因组计划拉开了精准医学时代的序幕，其本质是利用生物信息学、遗传学等技术，并整合患者临床资料，为不同生物学特征的患者提供精准化诊治。随着测序技术的发展，乳腺癌的精准治疗已逐渐渗透到肿瘤分子分型、靶向治疗以及外科手术等各个方面，以指导个体化的临床决策和治疗选择。     

乳腺癌微创消融研究进展

摘 要：微创和非手术方法在乳腺癌的治疗中越来越受到关注,而射频消融似乎是最具应用前景的微创治疗方式。然而,在实际使用射频消融治疗乳腺癌的研究中可能出现了一些亟待解决的问题,如缺乏合适的手段来准确评估消融灶边缘情况。国外一些可行性研究表明射频消融可以有效地清除乳腺癌细胞,这种技术对于乳腺癌的局部治疗是很有发展前景的,但目前国内仍处于初步研究阶段。文章主要对国内外射频消融治疗乳腺癌的研究进展及适应证等问题作一综述。     

肿瘤射频消融治疗的相关并发症及预防

目的总结肿瘤病人射频消融治疗的临床经验，对相关并发症及其预防进行探讨。方法分析200例肿瘤患者射频消融治疗的临床资料，观察和总结射频消融治疗后相关并发症的发生率、发生原因和预防措施。结果200例肿瘤病人射频治疗后其相关并发症发生率为20．5％，其中主要并发症18例（9％），其他并发症23例（11．5％），无严重并发症及死亡发生。结论射频消融是多种实体肿瘤的一种安全有效的微创治疗技术，加强管理、注重预防是避免和减少并发症的关键。     

循环肿瘤细胞在乳腺癌个体化诊治中的研究进展

循环肿瘤细胞从实体肿瘤病灶中脱离进入血液循环,携带了肿瘤细胞的特性,并且随疾病进展发生着改变,为临床上相对无创地获取肿瘤细胞样本提供了独有的机遇与挑战。近年来,大量的研究探索将循环肿瘤细胞应用于乳腺癌临床决策中,肯定了其在各期乳腺癌疾病进展及预后预测中的作用。同时,富集及检测技术的发展,为利用循环肿瘤细胞数目及其分子生物学特性进行疾病进展监测、药物疗效评估、指导乳腺癌个体化治疗选择以及寻找药物治疗新靶点带来了希望。现就循环肿瘤细胞在乳腺癌治疗决策中的最新研究进展予以简要综述。     

重视安全边界,提高肝癌射频消融的疗效

肝癌行射频消融治疗后肿瘤局部进展发生率较高,其主要原因为对安全边界的重视不够。射频消融治疗肝癌理想的目标是获得病理学完全消融,其消融范围应完全覆盖主体病灶、癌周微静脉浸润灶和卫星灶,形成足够的安全边界。全文就目前临床上射频消融治疗肝癌的标准、存在的问题及增加安全边界策略等问题作一探讨。     

氩氦刀冷冻消融治疗脑胶质瘤的现状与展望

胶质瘤是中枢神经系统难治性肿瘤，冷冻消融治疗作为一种新兴的肿瘤治疗技术在胶质瘤治疗中的价值正逐渐被重视。本文回顾了大量文献，从病理及分子生物学角度总结了冷冻消融治疗胶质瘤的机制；通过众多临床病例分析了冷冻疗法的适用范围、临床疗效和存在的问题；基于国内外前瞻性研究展望了冷冻治疗胶质瘤的发展方向及前景。冷冻消融可以通过直接导致坏死和凋亡、改变局部微循环和调节抗肿瘤免疫等机制摧毁肿瘤细胞；在影像学技术实时监控下冷冻可以成为很好的手术辅助手段，现已取得了满意的临床效果；另外冷冻技术与化疗、放疗、免疫治疗等方法联合应用可更有利于发挥其治疗作用。随着冷冻设备的改进和冷冻技术的完善，冷冻消融将在胶质瘤治疗中占有重要的地位。      

肝癌局部消融治疗技术及应用现状

近年来，针对肝癌的综合治疗日益发展，其中肝癌的局部消融治疗在其中显示越来越重要作用。因其具有疗效可靠、微创的特点，而且在安全性和疗效上也都取得了很好的效果。因而肝癌局部消融治疗为目前新的研究热点和肝癌治疗的重要手段。本文就目前现有肝癌局部消融治疗技术和临床应用情况加以概述，便于了解目前的应用现状。     

乳腺癌肝转移的机制及治疗进展

乳腺癌是女性最常见的恶性肿瘤,也是女性肿瘤相关性死亡的主要原因。乳腺癌发生远处转移是其死亡的主要原因之一,骨、肺、肝和脑是转移主要的靶器官;肝脏是实体肿瘤常见的转移部位,是乳腺癌第三常见的转移部位。乳腺癌肝转移的过程是多步骤的,是乳腺癌细胞和肝组织微环境中的多种因素共同参与的,进一步了解乳腺癌肝转移的机制对指导临床治疗至关重要。作者论述了乳腺癌肝转移的机制及治疗进展。     

射频消融抑制小鼠乳腺癌肺转移

目的：探讨射频消融术对小鼠三阴性乳腺癌肺转移和免疫系统的影响。方法小鼠乳腺癌4T1细胞系皮下接种于雌性Bal B／c小鼠右下肢处,肿瘤直径达到6～8 mm时进行射频消融治疗,流式细胞术检测脾脏中各淋巴细胞亚群的变化,观察肺转移的情况。结果射频消融基本上可以消除原位肿瘤,原位肿瘤复发率较低;射频消融后,小鼠脾脏CD4＋T细胞、CD8＋T细胞、B细胞、自然杀伤细胞及自然杀伤T细胞数量都有所升高;射频消融治疗4T1肿瘤14 d后,脱颈处死对照组和射频消融组小鼠,射频消融组和对照组4T1荷瘤小鼠的肺转移结节分别为（24±18）个和（81±35）个,差异有统计学意义（ P＝0．012）。射频消融抑制肺转移的机制与脾脏中CD4＋T细胞、CD8＋T细胞、B细胞和自然杀伤细胞的比例增加及髓系来源抑制细胞比例降低有关。结论射频消融增强了机体内抗肿瘤的免疫反应,抑制了小鼠4T1细胞乳腺癌的肺转移。射频消融术治疗三阴性乳腺癌和控制其远端转移可能会有良好的治疗效果。     

Body mass index,physical activity and the risk of pancreatic cancer in relation to smoking status and history of diabetes: a large-scale population-based cohort study in Japan–The JPHC study

Objective The effects of BMI and physical activity on the risk of pancreatic cancer were investigated in a large population-based cohort study in Japan (JPHC study). In particular, we explored how these effects were influenced by smoking status and a history of diabetes. Methods In total, 99,670 participants (47,499 men, and 52,171women) were followed for an average of 11 years through the end of 2003. Hazard ratios (HR) and their 95% confidence intervals (CI) were estimated by Cox proportional hazards models. Results A total of 224 incident cases (128 men, 96 women) of pancreatic cancer were identified. A statistically significant excess risk of pancreatic cancer was associated with current smoking (HR = 1.8, CI 1.1–3.0) and a history of diabetes (HR = 2.1, CI 1.3–3.5) among men. A similar increase in risk associated with current smoking (HR = 2.0, CI 0.9–4.4) and diabetes (HR = 1.5, CI 0.7–3.5) was also seen among women. BMI was inversely associated with risk of pancreatic cancer among men, especially among current male smokers or diabetes patients, but no association was found among women. Leisure-time physical activity was not associated with risk in either men or women. Conclusions Our study confirms the association between cigarette smoking, history of diabetes and increased risk of pancreatic cancer. However, our data suggest that the association between BMI and risk of pancreatic cancer in this Japanese population may be different from that in Western populations. Members of the JPHC Study Group (principal investigator: S. Tsugane): S. Tsugane, M. Inoue, T. Hanaoka and T. Sobue, National Cancer Center, Tokyo; J. Ogata, S. Baba, T. Mannami and A. Okayama, National Cardiovascular Center, Suita; K. Miyakawa, F. Saito, A. Koizumi, Y. Sano and I. Hashimoto, Iwate Prefectural Ninohe Public Health Center, Ninohe; Y. Miyajima, N. Suzuki, S. Nagasawa, Y. Furusugi and N. Nagai, Akita Prefectural Yokote Public Health Center, Yokote; H. Sanada, Y. Hatayama, F. Kobayashi, H. Uchino, Y. Shirai, T. Kondo, R. Sasaki, Y. Watanabe and Y. Miyakawa, Nagano Prefectural Saku Public Health Center, Saku; Y. Kishimoto, E. Takara, T. Fukuyama, M. Kinjo, M. Irei and H. Sakiyama, Okinawa Prefectural Ishikawa (Chubu) Public Health Centre, Ishikawa; K. Imoto, H. Yazawa, T. Seo, A. Seiko, F. Ito and F. Shoji, Katsushika Public Health Center, Tokyo; A. Murata, K. Minato, K. Motegi and T. Fujieda, Ibaraki Prefectural Kasama (Mito) Public Health Centre, Mito; K. Matsui, T. Abe and M. Katagiri, Niigata Prefectural Kashiwazaki Public Health Center, Kashiwazaki; M. Doi, A. Terao and Y. Ishikawa; Kochi Prefectural Tosayamada (Chuo-higashi) Public Health Center, Tosayamada; H. Sueta, H. Doi, M. Urata, N. Okamoto and F. Ide, Nagasaki Prefectural Arikawa (Kamigoto) Public Health Center, Arikawa; H. Sakiyama, N. Onga and H. Takaesu, Okinawa Prefectural Miyako Public Health Center, Hirara; F. Horii, I. Asano, H.Yamaguchi, K. Aoki, S. Maruyama and M. Ichii, Osaka Prefectural Suita Public Health Center, Suita; S. Matsushima and S. Natsukawa, Saku General Hospital, Usuda; S. Watanabe and M. Akabane, Tokyo University of Agriculture, Tokyo; M. Konishi and K. Okada, Ehime University, Matsuyama; H. Iso, Osaka University, Osaka; Y. Honda and K. Yamagishi, University of Tsukuba, Tsukuba; H. Sugimura, Hamamatsu University, Hamamatsu; Y. Tsubono, Tohoku University, Sendai; M. Kabuto, National Institute for Environmental Studies, Tsukuba; S. Tominaga, Aichi Cancer Center Research Institute, Nagoya; M. Iida and W. Ajiki, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka; S. Sato, Osaka Medical Center for Health Science and Promotion, Osaka; N. Yasuda, Kochi University, Kochi; S. Kono, Kyushu University, Fukuoka; K. Suzuki, Research Institute for Brain and Blood Vessels, Akita; Y. Takashima, Kyorin University, Mitaka; E. Maruyama, Kobe University, Kobe; M. Yamaguchi, Y. Matsumura and S. Sasaki, National Institute of Health and Nutrition, Tokyo; and T. Kadowaki, Tokyo University, Tokyo, Japan.     

Improvement of quality control for steroid receptor measurements: Analysis of distributions in more than 40000 primary breast cancers

Summary All French laboratories that routinely assay estradiol (ER) and progesterone (PR) receptors participate in the European EORTC quality control program based on twice-yearly analysis of 5 cytosolic preparations. This system has considerably reduced inter-laboratory variations, but does not cover all aspects of these assays. Analysis of receptor value distributions is also crucial to ensure that receptor measurements remain stable with time, independently of the laboratory and assay method. This study involved 83907 receptor assays carried out in the last 17 years by 17 laboratories belonging to the French Study Group on Tissue and Molecular Biopathology. The assays were based on radioligand binding (RLA) or immunoenzymology (EIA). For each laboratory, the medians and positivity rates were analysed according to two totally objective criteria, the patient's age and the year of assay, and according to histological grade and histological type of the tumor in order to verify the correlations classically described. Age-related distributions varied little between laboratories, compared with data published by 7 European EORTC laboratories [1]. The results remained relatively stable with time in the RLA method for ER and PR, and in the EIA method for PR. Median ER-EIA data showed a marked increase between 1987 and 1989, mainly due to changes in the quality of Abbott reagents during this period. Otherwise, this analysis confirms previous pathophysiological observations.List of participants: J.P. Basuyau, P. Brunelle, Centre Henry Becquerel, Rouen; G. Besse, Centre Jean Perrin, Clermond Ferrand; E.M. Chambaz, M. Chedin, S. Bottari, CHRU, Grenoble; A. Daver, Centre Paul-Papin, Angers; J.C. Delarue, Institut Gustave Roussy, Villejuif; J. Goussard, Centre François Baclesse, Caen; J. Grenier, CRLCC Val d'Aurelle, Montpellier; J.C. Jardillier, A. Rallet, Institut Jean Godinet, Reims; P. Jolliet, Centre Intercommunal, Creteil; M. Lanson, P. Bougnoux, CHU Bretonneau, Tours; H. Magdelénat, Institut Curie, Paris; P.M. Martin, S. Romain, Faculté de Médecine Nord, Marseille; G. Milano, J.L. Formento, Centre Antoine Lacassagne, Nice; J.P. Peyrat, Centre Oscar Lambret, Lille; V. Quillen-Pouvreau, Centre E. Marquis, Rennes; G. Ricolleau, Centre René Gauducheau, Saint-Herblain; H. Rochefort, J.P. Brouillet, Hôpital A. de Villeneuve, Montpellier; G. Soula, P. Courrière, Centre Claudius Regaud, Toulouse; F. Spyratos, Centre René Huguenin, Saint-Cloud; J. Wafflart, Fondation Bergonié, Bordeaux.     

Book Reviews

1990 Recommendations of the International Commission on Radiological Protection Pergamon Press pic, Oxford, England. ISBN: 0 08 0411444 GBP 80.-

Breast Diseases, 2nd edition J. R. Harris, S. Hellman, I. C. Henderson, D. W. Kinne, eds. J. B. Lippincott Company, Hagerstown, USA, 1991, 960 pp. ISBN: 0-397-51079-9 USD 186.95.-

Risk Assessment in Chemical Carcinogenesis G. Schettler, D. Schmahl, T. Klenner, eds. Springer-Verlag, Berlin, 1991, 172 pp. ISBN: 3-540-54149-7 DM49.-

New Drugs, Concepts and Results in Cancer Chemotherapy F. M. Muggia, ed. Kluwer Academic Publishers, Dordrecht, The Netherlands, 1991, 165 pp. ISBN: 0-7923-1253-8 GBP59.75.-.Hardback

Practical Radiotherapy Planning. 2nd edition J. Dobbs, A. Barrett, D. Ash, eds. Edward Arnold, UK, 1992, 303 pp ISBN: 0-340-54557-7 GBP24.95.-. Paperback

Manual for Clinical Research in Breast Cancer EORTC Breast Cancer Cooperative Group. c/o EORTC Breast Cancer Secretariat, Department of Radiotherapy, Academisch Ziekenhuis St. Raphael, Capucijnenvoer 35, B-300 Leuven, Belgium BEF50.-.     

Book Reviews

Book reviewed in this article: An Atlas of Lower Limb Ischaemia, by T. S. Weston and S. E. Brooks. Pp. 40, The Princess Margaret Hospital, Christchurch, New Zealand, 1976. Computerised Axial Tomography: J. Gambarelli, G. Guerinel, L. Cheverot, M. Mattei, (Springer-Verlag, New York, 1977). Cross-Sectional Anatomy: Computed Tomography & Ultrasound Correlation, Barbara L. Carter, James Moorehead, Samuel M. Wolpert, Steven B. Hammerschlag, Harry J. Griffiths and Paul C. Kahn. (Appleton Century Crofts, New York, 1977). Dynamic Radiology of the Abdomen: Normal and Pathological Anatomy, Meyers, A.M. (Springer-Verlag, New York, 1976). Radiology of the Abdomen: Anatomic basis: Joseph P. Whelan, (Lea & Febiger, 1976. Philadelphia).     

基于文献分析的精准乳腺癌个体化医疗进展研究

目的　根据近5年乳腺癌精准医学和个体化医学相关文献，分析其国内外研究进展，探究个体化医疗的现状和未来的发展方向，构建以患者为中心的乳腺癌个体化医疗方案。方法　抽取万方医学网（限定中国科技核心期刊）和Web of Science 两个数据库中的乳腺癌精准相关文献，对其进行统计分析，从年发文趋势、国家、研究机构、国内外热门研究领域与高频关键词分布等角度入手。结果　共检索到精准医学相关中文文献3 336篇，英文文献20 241篇，近5年乳腺癌在精准医学方面的文献呈总体上升趋势；发文量最大的国家为美国（30.4％），其次是中国（24.0％）；国内高发文机构为中国科学院系统（295 篇／1.415％）；研究热点主要表现为通过液体活检和新一代基因测序实现精确诊断，通过靶向用药、精准外科和免疫治疗实现精确治疗。精准医疗更重视“病”的深度特征和“药”的高度精确性，形成高水平医疗技术。结论　精准医学是实现个体化医学的基础和必须条件。乳腺癌精准医学的研究以实现个体化医学为目标，以基因测序和靶向药物为基础，结合遗传因素、环境因素、药物反应个体差异，并考虑年轻乳腺癌保乳治疗等复杂议题，因此现代个体化医学应当逐渐形成以患者为中心，了解自身基因，针对性改善外部环境，从而形成个体化治疗和用药的医疗模式，进而预防疾病发生，提高生活质量。但是目前的个体化医学仍面临严峻的挑战，需要我们共同的努力。     

Prognostic factors for high-grade malignant glioma: Development of a prognostic index

Summary Although the prognosis of high grade malignant glioma patients is generally poor, it is possible to identify groups of patients with varying prognoses. Basing our results on the first MRC glioma study, multivariate methods were used to identify prognostic factors independently associated with the length of survival. Young age, the presence of fits, especially of long duration, extensive surgical removal of tumour and good clinical performance status were found to be the most important predictors of longer survival. The effect of tumour grade (3 or 4) was not significant, being considerably diluted by an association with extent of neurosurgery. A prognostic index was derived which split the patients into 6 groups of varying prognoses, with 2-year survival rates of between 1 and 32%. The results were verified in patients entered into a subsequent MRC trial. The successful identification of different prognostic groups suggests the use of this index as an aid in making treatment decisions for individual patients, and in interpreting the results of uncontrolled phase II studies.This report was prepared on behalf of the participating members by S.P. Stenning, L.S. Freedman (statisticians) and N.M. Bleehen (Chairman). The following clinicians and their colleagues participated in the Misonidazole or BR2 studies and/or are members of the Brain Tumour Working Party: G.E. Adams, A.M.A. Ayoub Bey, R.O. Barnard, J. Bozzino, J.D. Bradshaw, T.B. Brewin, J. Bullimore, D.P. Dearnaley, P. Gortvai, N.F.C. Gowing, A. Gregor, J.M. Henk, H.F. Hope-Stone, A. Hovenden, N. Howard, H. Hughes, A. Jones, R.M. Kalbag, I. Kerby, V. Levin, A.R. Lyons, D.S. Murrell, M.J. Ostrowski, C.E. Polkey, R. Rampling, R.I. Rothwell, P.F. Salaman, C. Scholtz, J.S. Scott, R. Sealy, L.F.N. Senanayake, B. Southcott, J. Stone, H.M. Sultana, B.E. Tomlinson, C.S. Treip, S. Vaidya, P. Wale, P.J. Winter, P. Xavier. Data management was carried out by Mrs. Bethan Smith.     

免疫组化标记物在子宫内膜样腺癌与宫颈腺癌鉴别诊断中的表达及意义

目的探讨免疫组化标记物波形蛋白(Vimentin)、癌胚抗原(CEA)、雌激素受体(ER)、孕激素受体(PR)和p16蛋白在子宫内膜样腺癌与宫颈腺癌鉴别诊断中的表达和意义。方法采用免疫组织化学染色法检测48例子宫内膜样腺癌和21例宫颈腺癌患者肿瘤组织中Vimentin、CEA、ER、PR和p16的表达,并分析其临床意义。结果子宫内膜样腺癌患者肿瘤组织中Vimentin、CEA、ER、PR和p16阳性表达率分别为79.2%、31.3%、87.5%、81.3%和20.8%。宫颈腺癌患者肿瘤组织中Vimentin、CEA、ER、PR和p16阳性表达率分别为14.3%、90.5%、23.8%、42.9%和81.0%。经2检验,Vimentin(2=25.50)、CEA(2=20.50)、ER(2=27.29)、PR(2=10.17)和p16(2=22.17)在子宫内膜样腺癌和宫颈腺癌患者肿瘤组织中阳性表达率的差异均有统计学意义(P<0.05)。结论免疫组化法检测Vimentin、CEA、ER、PR和p16的表达有助于临床鉴别诊断宫颈腺癌和子宫内膜样腺癌。     

79例肺肉瘤样癌的临床特征及预后分析

目的 通过分析肺肉瘤样癌（pulmonary sarcomatoid carcinoma, PSC）的临床资料,探讨其临床特征及预后因素。方法 回顾性分析79例PSC患者的临床资料,采用SPSS19.0统计软件对患者的性别、年龄、是否有吸烟史、肿瘤的原发部位、位置类型、肿瘤大小、T分期、有无淋巴结转移、有无远处转移、TNM分期、组织学亚型、治疗方法及是否手术等因素进行预后分析。采用Kaplan-Meier法进行生存分析,采用Log rank法进行单因素分析,采用Cox比例风险回归模型进行多因素分析。结果 与腺癌、鳞癌、小细胞癌等肺癌亚型相似,PSC患者多以咳嗽、胸闷、发热、痰中带血、咯血、胸痛等为初诊症状。本研究中患者的1、2、3年总生存率分别为25.3%、8.0%、4.8%,中位生存时间为8.0月。单因素分析显示,年龄、肿瘤大小、T分期、有无远处转移、TNM分期、治疗方法及是否手术是影响预后的因素。结论 PSC是一类少见的、侵袭性较高的非小细胞肺癌,预后差。与其他肺部肿瘤相比,PSC缺乏典型的临床表现,诊断主要依靠病理学和免疫组织化学方法。本研究中患者的年龄、肿瘤大小和治疗方法是影响预后的独立因素,手术联合放化疗是首选治疗方法。