Outcomes in Patients Treated[PMIDA23195778]

合集下载

癌症的过度诊断英语作文

癌症的过度诊断英语作文In recent years, the issue of cancer overdiagnosis has become a significant concern in the medical community. Overdiagnosis occurs when a cancer is diagnosed that would not have caused any symptoms or harm during a person's lifetime. While early detection of cancer is crucial for effective treatment, overdiagnosis can lead to unnecessary stress, invasive treatments, and healthcare costs.One of the primary reasons for cancer overdiagnosis is the increased use of advanced screening technologies, such as mammograms for breast cancer and PSA tests for prostate cancer. These screenings have improved our ability to detect cancer at earlier stages; however, they also lead to the identification of slow-growing tumors that may never progress to a life-threatening stage. This is particularly evident in prostate cancer, where many men diagnosed may not require immediate treatment.The psychological impact of overdiagnosis should not be underestimated. Patients who receive a cancer diagnosis often experience anxiety and fear, even iftheir cancer is not aggressive. The label of "cancer" can lead to emotional distress and a diminished quality of life. Furthermore, the treatments for cancer, such as surgery, radiation, or chemotherapy, can have significant side effects and may not be necessary for patients with non-aggressive tumors.To address the issue of overdiagnosis, it is essential to promote informed decision-making among patients and healthcare providers. Patients should be educated about the risks and benefits of cancer screenings, as well as the possibility of overdiagnosis. Healthcare providers must engage in shared decision-making, considering the individual patient's values and preferences when recommending screenings and treatments.In conclusion, while early detection of cancer is vital, we must be cautious about the risks of overdiagnosis. By fostering awareness and encouraging informed choices, we can help patients avoid unnecessary treatments and improve their overall well-being.中文翻译：近年来，癌症过度诊断的问题在医学界引起了广泛关注。

从中医药核心结局指标集研究反观干预措施在核心结局指标集的地位

•研究报告•从中医药核心结局指标集研究反观干预措施在核心结局指标集的地位万颖、刘长信\周彦吉、张英、孙亚男2,于长禾1y北京中医药大学东直门医院，北京100700; 首都医科大学宣武医院中医科，北京100053)摘要：核心结局指标集（C O S)研制过程中，由丁•默认C O S对结局指标的选择受到十预措施的影响，出现了“在持定健康状态下，根据干预措施的不同而制定不同C O S的情况”针对建立具有中医药特色的结局指标的观点，本课题组认为：结局指标的本质是反映受试行的健康状态或状态变化，特定人群中评价结局指标测量T_具优劣的指标是信度.效度，结局指标的差异是中国与国外文化差异，而不是中医与西医的差别，因此结局指标的选择应该根据患者'需求设_、>:而不是十预措施针对建立具有中医药c o s的观点，本课题组认为：的概念中体现“核心”“所有临床研究”“最小集合”等关键时，要求不同干预下建立相同的c o s,以方便横向比较；c o s提出“特定健康状态”说明了特定患者群体认为重要或者期望的结局是核心结局，而且C U S制定时W求限制十预制造商的参与比例以避免a)s研究中的利益冲突和偏倚.据此，否定丫建立中医药(:o s的假设经过分析结局指标的分类后，课题组提出迮立与患荇特定健康状态相关的核心结局指标集（p a-c o s)和与干预措施相关的特色结局指标集（I n-S O S)的新体系，以解决当前核心结局指标*研究的困境，并为C O S的发展#找新途径，建立新方法学体系。

关键词：核心；特色；结局；干预；方法学；中医药；核心结局指标集基金资助：国家A然科学基金青年科学基金项目（N(1.81803956 )Introspection on the position of intervention in the core outcome sets development fromstudying the core outcome sets of traditional Chinese medicineWAN Ying1,LIU Chang-xin1,ZHOU Yan-ji1,ZHANG Ying1,SUN Ya-nan:,YU Chang-he1 ('Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700. China: 'Traditional Chinese MedicineDepartment. Xuanwu Hospital, Capital Medical University, Beijing 1(X)()53, China )Abstract：During the development of the core outcome sets (COS), due to the influence of the default COS selection of outcomes by the intervention, there was a situation in which ^different COS was developed depending on the intervention ina specific condition'. In view of the idea of establishing the COS with the characteristics of Chinese medicine, the project teamindicates that: the essence of the outcomes is to reflect the health condition or its change of the subject, the index of evaluatingthe measurement instruments of the outcomes in a particular population is the internal consistency, content validity and criterionvalidity. And the difference of the outcomes consists in Chinese and foreign cultural adaption, not the difference between Chinesemedicine and Western medicine. The choice of outcomes should therefore be based on patients' demands rather than interventions.In view of the idea of establishing COS of Chinese medicine, the project team holds that: the concept of COS embodies the'core', all clinical studies', 'minimum set' and other keywords, which requires different interventions to establish the same COSto facilitate horizontal comparison, explains that the core outcomes are what certain patient population considered important ordesired to be. COS is developed to limit the participation of intervention manufacturers to a lower percentage of participation toavoid conflicts of interest and bias in COS research. According to this, the hypothesis of establishing COS in Chinese medicineis rejected. After analyzing the classification of outcomes, the project team proposed the establishment of a new system whichconsists of core outcome sets related to participants (participant-related COS, pa-COS) and specific outcome sets related to通信作者：于长禾，北京市东城K海运仓5兮北京中民药大学东直门陕院推拿疼痛科，邮编：100700，电话：************E-mail ：vakno2@ 163.r〇minterventions (intervention-related specific outcome sets. In-SOS) to solve the current dilemma in COS studies, and to find new ways to promote the development of COS as well as establish a new system of methodology.K e y W O rdsi Core; Characteristic; Outcome: Intervention: Melhtxlology; Traditional Chinese medicine; Core outcome sets (COS) Funding：Young Scientists Fund of National Natural Science Foundation of China (N〇.81803956)核心结局指标集（core o u t c o m e sets，C O S)是指特定健康领域的所有临床研究中必须报告的最小指标集合，即业界公认的临床结局、结局指标及其测量方法和测量时间点等的最小集合111,C O S能规范化、标准化结局指标及其测量T.具，减少发表偏倚或结局指标选择性报告，提高不同十预横向比较及不同研究纵向M e/a分析12M有效性试验核心结局指标（core o u t r o m e measures in effectiveness trials，C O M E T)工作组制定的《C O M E T 操作手册1.0版》141中提出根据不同的干预措施制定(:o s,即建立同一疾病不同干预下的c o s中医药存在结局指标多、指标测M T具混乱、缺少终点指标等问题，因此国内很多学者提出建立中医药相关疾病的c o s|S_81:但从c o s的概念不难发现，建立的c o s是普适的、非干预针对性的结局指标，仅与患者的“特定健康”相关，而与患者接受的何种干预是无关的例如，在有关心血管试验的c o s研究中，中医药治疗稳定性心绞痛的c o s研究151和非瓣膜性房颤中医临床C O S研究161前者最终确定的排名前15位的结局指标中包括心绞痛相关指标（心电图疗效、心绞痛疗效、心绞痛发作次数、心绞痛持续时间、硝酸甘油停减率/用量、血脂、血液流变学指标等）、生活质量（西雅r a心绞痛量表）、不良反应、安全性指标、中医证候评价指标（中医证候疗效、中医证候积分、中医症状积分）等；后者最终确定的结局指标包括：房颤首次复发时间、房颤转复率、心血管病死率、脑血管事件、血栓栓塞事件、生活质M、不良反应、急诊就诊率、治疗依从性、中医证候等对比以上结果可发现，两个研究除了证候相关结局指标，其他指标均为现代医学的结局指标，间接说明中医药c o s的特色指标是证候相关评价指标，其他指标与现代医学相同，相同的对比结果在糖尿病视网膜病变、慢性乙型病毒性肝炎等疾病上也有所发生|7-91。

急性间质性肺炎一例并文献复习

·研究论著·急性间质性肺炎一例并文献复习巴俊慧石云锋冯定云吴本权【摘要】目的探讨急性间质性肺炎（AIP）的病因、诊断与治疗，提高对该病的认识水平。

方法对1例一氧化碳中毒后迟发性脑病患者发生AIP的临床资料进行回顾性分析，并以“急性间质性肺炎”或“acute interstitial pneumonia”为检索词在PubMed、中国期刊全文数据库（CNKI）、万方数据知识服务平台和维普中文科技期刊数据库检索，收集并分析检索到的有详细症状、诊断、治疗、转归的病例资料。

结果该例为21岁的一氧化碳中毒后迟发性脑病女性患者，因呼吸衰竭转入内科ICU，经抗感染治疗无效，病理活组织检查（活检）诊断为AIP，予肾上腺皮质激素（激素）、环磷酰胺、机械通气等治疗后好转出院。

检索文献后，排除已知AIP诱发因素的病例，157例有详细症状、诊断、治疗、转归的病例资料，其中72例经病理活检确诊。

AIP患者的主要临床表现为咳嗽（141例，89.8%）、呼吸困难（130例，82.8%）、发热（79例，50.3%），主要影像学表现为磨玻璃样变（119例，75.8%）、肺实变（37例，23.6%）、弥漫性渗出影（33例，21.0%）；主要病理活检表现为Ⅱ型肺泡上皮增生（24例，33.3%）、肺泡纤维化（22例，30.6%）、肺泡间隔增厚（20例，27.8%）；使用大剂量激素治疗44例（28.0%），联合免疫抑制剂治疗12例（7.6%），行机械通气100例（63.7%）；体外膜肺氧合（4例，2.5%）；共57例（36.3%）患者好转出院，100例（63.7%）患者死亡。

结论AIP是一种病因未明、起病急骤、以呼吸衰竭为主的间质性肺炎，目前无疗效确切的治疗方法，早期激素治疗可能有效，临床预后差。

【关键词】急性间质性肺炎；肺损伤；高压氧Acute interstitial pneumonia：one case report and literature review Ba Junhui，Shi Yunfeng，Feng Din⁃gyun，Wu Benquan.Medical Intensive Care Unit，the Third Affiliated Hospital of Sun Yat⁃sen University，Guangzhou510630，ChinaCorresponding author，Wu Benquan，E⁃mail：【Abstract】Objective To analyze the pathogenesis，diagnosis and treatment of acute interstitial pneu⁃monia（AIP）and deepen the understanding of AIP.Methods Clinical data of one patient with delayed en⁃cephalopathy suffering from AIP after carbonic oxide poisoning were retrospectively analyzed.A comprehensive literature search was performed in PubMed，China Journal Full⁃text Database（CNKI），Wanfang Data and Chongqing Vip database using the keywords of"acute interstitial pneumonia"in both English and Chinese.De⁃tailed clinical data including symptoms，diagnosis，treatment and outcomes of patients with AIP were collectedand analyzed.Results The21⁃year⁃old female patient diagnosed with delayed encephalopathy was transferred tothe MICU due to respiratory failure after carbonic oxide poisoning.She was not effectively treated after antibiotic therapy.She was diagnosed with AIP by pathological tissue examination（lung biopsy）,Then，the patient wastreated with steroid，cyclophosphamide，and mechanical ventilation.She was recovered and discharged.After excluding patients whose inducing factors of AIP have been identified，detailed symptoms，diagnosis，treat⁃ment and outcomes were collected from157AIP patients，and72cases of them were confirmed by pathological biopsy.The clinical manifestations of AIP patients mainly included cough（n=141，89.8%），dyspnea（n=130，82.8%）and fever（n=79，50.3%）.The main imaging findings consisted of ground glass changes（n=119，75.8%），pulmonary consolidation（n=37，23.6%）and diffuse exudative lesions（n=33，21.0%）.DOI：10.3969/j.issn.0253⁃9802.2018.12.010基金项目：广东省科技计划项目（2017A020215177）作者单位：510630，广州，中山大学附属第三医院内科ICU（巴俊慧，石云锋，吴本权），呼吸内科（冯定云）通讯作者，吴本权，E⁃The dominant pathological findings were typeⅡalveolar epithelial hyperplasia（n=24，33.3%），alveolar fi⁃brosis（n=22，30.6%）and thickening of alveolar septum（n=20，27.8%）.Forty⁃four cases（28.0%）were treated with high⁃dose hormone therapy，12（7.6%）were supplemented with immunosuppressive agents，100（63.7%）received mechanical ventilation and4cases were treated with ECMO（2.5%）.A total of57 patients（36.3%）were recovered and discharged，whereas100patients（63.7%）died.Conclusions AIP is a category of interstitial lung disease with unknown pathogenesis，urgent onset which rapidly develops in⁃to respiratory failure.At present，there is no exactly effective treatment.Early steroid therapy may be beneficial to patients，but the clinical prognosis of AIP patients is rather poor.【Key words】Acute interstitial pneumonia；Lung injury；Hyperbaric oxygen急性间质性肺炎（AIP）是临床中罕见的、发展迅速的暴发性肺损伤，患者可急进性出现通气功能障碍和呼吸衰竭，病死率可达50%以上。

药学英语药学英语35

❖ Thus, surrogate outcomes are less desirable measures of efficacy than patient-oriented outcomes.
❖ 同样，如果替代结果仅仅是一个疾病的高)，那么一种干预措施可能降低指标但并不影响基础疾病。
❖ However, it is conceivable 可以想象的 that a drug could lower BP but not decrease mortality, perhaps because it has fatal adverse effects.
❖ 例如，临床医生通常认为降低血压将防止顽固性高血压的以患者为中心的结果(例如，心梗或中风导致的死亡)。
❖ 在这种情况下，需要进行大型的、长期的临床试验，除非采用替代结果(例如，低血压)。
❖ In addition, the main patient-oriented outcomes, death and disability, are dichotomous (i.e., yes/no); whereas surrogate outcomes are often continuous, numerical 数字的 variables (e.g. BP, blood glucose).
患者为中心的结果指的是那些影响患者健康的结果。它们包括以下几点: ❖ 寿命延长 ❖ 功能改善(例如，预防出现残疾) ❖ 症状缓解。
Surrogate outcomes 替代结果
❖ Surrogate or intermediate outcomes involve things that do not directly involve patients well being.

2022年考研考博-考博英语-全国医学统考考试全真模拟易错、难点剖析B卷(带答案)第21期

2022年考研考博-考博英语-全国医学统考考试全真模拟易错、难点剖析B卷（带答案）一.综合题(共15题)1.单选题As a nurse, Dorothy is a natural healer who is endowed with compassion and has a variety of modalities to benefit her patients of all ages.问题1选项A.braveryB.expertiseC.proficiencyD.sympathy【答案】D【解析】【选项释义】A. bravery 勇敢B. expertise 专门知识；专门技术C. proficiency 精通；熟练D. sympathy 同情；慰问【答案】D【考查点】名词辨析。

【解题思路】由本句句意可知作为一名护士，所应该有的是同情心以及专业的知识，而从前半句中的“natural healer（天生的治疗师）”可知天生所拥有的是同情心，所以D选项“同情，慰问”符合题意。

划线单词compassion“同情”。

【干扰项排除】A选项bravery勇敢，与护士治疗病人无关，不符合句意；B选项expertise专门知识；专门技术，因为说的是天生的治疗师，因此应该是天生所具有的品格，专门知识是后天所拥有的；C选项proficiency精通；熟练，这也是后天才具备的，不符合句意。

【句意】作为一名护士，多萝西是一个天生的治疗师，她被赋予了同情心，有各种各样的方式来帮助她的所有年龄的病人。

2.单选题Many problems that we face, such as depression, compulsive and addictive behaviors, and anxiety, result from human inherent desire to seek pleasure.问题1选项A.consecutiveB.excessiveC.obsessiveD.possessive【答案】C【解析】【选项释义】A. consecutive 连贯的；连续不断的B. excessive 过多的C. obsessive 强迫性的；着迷的D. possessive 占有的；所有的【答案】C【考查点】形容词辨析。

《患者报告结局在药物临床研究中应用的指导原则(征求意见稿)》

2021年9月目录一、引言 (1)二、患者报告结局的定义 (1)三、患者报告结局测量量表的研发、翻译、改进 (2)（一）患者报告结局测量量表的研发 (3)（二）用于患者报告结局测量量表的翻译和/或文化调适 (7)（三）患者报告结局测量量表的改进 (9)四、患者报告结局测量量表的选择与评价 (9)五、临床研究中使用患者报告结局的考虑 (11)（一）估计目标框架 (11)（二）选择患者报告结局作为临床研究终点 (11)（三）研究方案和研究报告中有关量表的阐述 (12)（四）量表的有效应答 (12)（五）缺失数据 (13)（六）多重性问题 (14)（七）结果的解释 (14)（八）PRO/ePRO的质量控制 (15)（九）真实世界研究中PRO/ePRO的使用 (16)六、电子化患者报告结局 (16)（一）ePRO测量 (16)（二）使用ePRO的一般考虑 (17)七、与审评机构的沟通交流 (19)参考文献 (20)附录1：词汇表 (22)附录2：中英文词汇对照 (26)123一、引言4临床结局是评价药物治疗获益与风险的核心依据，如何5准确、可靠、完整地观测临床结局至关重要。

患者报告结局6(patient-reported outcome，PRO)是临床结局的形式之一，在药7物注册临床研究中得到越来越广泛的使用。

另外，随着以患8者为中心的药物研发的理念和实践的不断发展，在药物全生9命周期中获取患者体验数据并将其有效地融入到药物的研10发和评价中日益受到重视，而PRO也是其中的一个重要组11成部分。

12本指导原则旨在阐明PRO的定义以及在药物注册研究13中的适用范围，PRO测量特别是量表研发和使用的一般原则，14PRO数据采集的质量控制，数据分析和解释需要注意的事项，15以及与监管部门的沟通等，为申办者提供药物注册研究中合16理使用PRO数据提供指导性意见。

17本指导原则适用于使用PRO作为终点指标支持药品注18册的临床研究，包括临床试验和真实世界研究。

乳头状及滤泡状甲状腺癌术后如何选择性应用放射性碘治疗

Journal of Surgical Oncology2006;94:692–700 Selective Use of Radioactive Iodine in the Postoperative Management of Patients With Papillary andFollicular Thyroid CarcinomaIAN D.HAY,MB,PhD,FACP,FRCP*{Mayo Clinic College of Medicine,Endocrinology and Internal Medicine,Mayo Clinic,Rochester,MinnesotaRadioiodine remnant ablation(RRA)was developed in the1960s to‘‘complete athyroidectomy’’in the initial management of papillary and follicular thyroid cancer.By the1990s,it was claimed that RRA diminished recurrence rates in follicular cell-derived cancer(FCDC)patients and decreased the cause-speciﬁc mortality(CSM)inpatients more than40years old at initial surgery.The international trend for the pastdecade has been towards routine RRA in most FCDC patients.Clinical guidelineshave been produced by many societies,promoting such an aggressive stance.Since1997,many papers have reported improved outcome in FCDC,when patients weresubjected to RRA after bilateral lobar resection.However,during the same time-period,it has been recognized that most FCDC patients are truly at‘‘low-risk’’ofdeveloping life-threatening recurrences.Accordingly,it has been suggested thatrational therapy selection should lead to restricting aggressive therapy to those‘‘high-risk’’FCDC patients,more predisposed to CSM.To date,no prospective controlledtrials exist.Presently available outcome data is based on single institutional ormulticenter retrospective studies.This article summarizes the available relevantreported data,and concludes that a selective use of RRA in the postoperativemanagement of FCDC patients is rational,and should actually be encouraged.J.Surg.Oncol.2006;94:692–700.ß2006Wiley-Liss,Inc.K EY W ORDS:remnant ablation;differentiated thyroid cancer;postoperativeradioiodine;cause-speciﬁc mortality;tumor recurrence;outcome predictionINTRODUCTIONIn the United States,papillary thyroid carcinoma (PTC)during the past three decades has accounted for between80%[1]and88%[2]of patients with thyroid malignancy.PTC is associated typically with a20-year cause-speciﬁc mortality of only5%,whereas in most recent studies,the less common follicular thyroid cancer (FTC)and Hurthle cell cancer(HCC)have higher20-year mortality rates in the15%–25%range[3].Radio-active iodine(RAI)wasﬁrst used to treat metastatic follicular cell-derived cancer(FCDC)in1940[1].The concept of remnant ablation to‘‘complete thyroidect-omy’’derives from the early1960s,and by the late1980s, it was reported to decrease postoperative recurrences, when compared with surgery and thyroid hormone suppression alone[4].During1997–2001,it was further claimed that radioiodine remnant ablation(RRA)effec-tively reduces recurrences of FCDC in all patients and decreases the mortality rate in patients more than age 40years at the time of diagnosis[5,6].During the past two decades,it has been increasingly recognized that between70%and88%of PTC patients may be classiﬁed at presentation as‘‘low-risk’’on the basis of prognostic factors established by multivariate analyses of large cohorts of treated patients[7–10].PTC patients who are,at presentation,pTNM stages I or II, AMES low-risk,or have MACIS scores less than6,enjoy a1%cause-speciﬁc mortality(CSM)at20postoperative {Richard F.Emslander Professor in Endocrinology Research,Professor of Medicine,and Consultant in Endocrinology and Internal Medicine.*Correspondence to:Ian D.Hay,Mayo Clinic College of Medicine, Endocrinology and Internal Medicine,Mayo Clinic,Rochester,Minnesota 55905.Fax#:507-284-5745.E-mail:hay.ian@Received23August2006;Accepted28August2006DOI10.1002/jso.20696Published online in Wiley InterScienceyears.By contrast,the12%–30%of patients classiﬁed as ‘‘high-risk’’by pTNM,AMES,or MACIS,have CSM rates25–40times higher than the‘‘low-risk’’patients [7–10].A logical extension of a belief in risk-group assignment in FCDC would naturally lead to an application of‘‘rational therapy selection’’in this commonest of endocrine malignancies[9,11–13]. Indeed,as Blake Cady has repeatedly emphasized,in the management of patients with low-risk PTC,the ‘‘punishment shouldﬁt the crime’’[7,9].Unfortunately, in the past decade this has not been the therapeutic trend. Sadly,since1996,many specialist societies in the United States and in Europe have published guidelines for the treatment of DTC,where it is recommended that almost all patients with FCDC more than1cm in diameter will receive radioactive iodine-131for post-operative RRA[14–16].It is claimed that such an aggressive management program will eliminate mortality and further reduce recurrence at local and distant sites. During this same time-period,it is noteworthy that few surgical centers in the United States have had the opportunity of comparing eras,where surgery and thyroid hormone therapy alone was usual(1950–1974),as opposed to the last quarter of the past century(1975–2000),where RRA was increasingly employed for FCDC therapy.In the past5years,analysis has been completed on the outcome results of2,512PTC patients consecutively treated at the Mayo Clinic during the period from1940to 2000[11,12].During that period,encompassing more than six decades,there were two signiﬁcant therapeutic trends(Fig.1).Theﬁrst was a change in surgical practice during1940–1969from unilateral lobectomy to bilateral lobar resection.The second trend was the increased use since1970of radioactive iodine-131for RRA.The results derived from further examination of these two trends have far-reaching implications reaching far beyond Olmsted County,Minnesota[17],and have certainly resulted in recent changes in practice at Mayo Clinic with regards to the initial management of patients with low-risk PTC.In this contribution for Seminars in Surgical Oncology the early history and more recent claims for efﬁcacy of RRA will be described.A typical case of low-risk PTC will be presented,and the questions raised in the postoperative management will be addressed by evi-dence-based answers,derived from the results of recently completed Mayo outcome analyses.Thereafter,the recent results of large national and multicenter studies from Canada and the USA will be brieﬂy discussed and placed in perspective.ORIGINS,EARLY CLAIMS,AND LATERDISCLAIMERS FOR REMNANT ABLATIONIn1940,Hamilton and his UCSF associatesﬁrst reported the uptake of RAI in a thyroid carcinoma[18], and by1942Keston described theﬁrst treatment of a patient’s iodophilic femoral metastasis with a10mCi therapeutic dose[19].By1960,Blahd and his UCLA colleagues had given11FCDC patients RAI to ablate postoperative remnant tissue in an attempt to‘‘complete the thyroidectomy’’[20].At the Mayo Clinic,during 1950–1969,patients with PTC,who had either gross residual disease or initial distant metastases,regularly received postoperative RAI in therapeutic doses.How-ever,of568PTC patients having initial potentially curative bilateral surgery during that20-year period,only 19(3%)received within6postoperative months a dose of RAI aimed at ablating the residual thyroid remnant[1].In 1970,a group from the University of Michigan reported that84patients with FCDC,who were aged40years and older,and were treated with surgery followed by RAI, experienced a signiﬁcantly lower mortality rate than32 controls who had surgery alone[21].However,in this report the extent of disease was not controlled and the so-called control group came from an earlier period(1933–1947)marked by less aggressive surgery[3]. Although RAI therapy is clearly indicated and often beneﬁcial for patients with local or distant residual disease[22,23],the use of RRA,which has been deﬁned as‘‘the destruction of residual macroscopically normal thyroid tissue following surgical thyroidectomy’’[24]in low-risk patients remains highly controversial.Less controversial is RRA in patients with high-risk PTC, who are more likely to beneﬁt from RRA in terms of decreased disease progression and mortality[25].The goals of RRA are said to be threefold:(1)to destroy any occult microscopic carcinoma cells within the thyroid remnant,(2)to facilitate RAI scanning for detection of recurrent or metastatic disease by destruction of remain-ing normal tissue,and(3)to improve the value of serum Tg as a tumor marker in follow-up[14].In addition,theFig.1.Trends in the(left panel)extent of initial surgery,and(rightpanel)the proportion of PTC patients having radioiodine remnantablation after initial bilateral lobar resection at Mayo Clinic during1940–2000.Selective Use of Postop Radioiodine693use of a large amount of RAI for therapy allows for obtaining a postablative whole body scan(WBS)with increased sensitivity for persistent disease detection[26]. Mazzaferri and his US Air Force study of1977 signiﬁcantly inﬂuenced the worldwide treatment of PTC, and the implications of his message are still widely debated today.In1977,he reported lower recurrence rates in114PTC patients receiving thyroid hormone and RAI therapy,when compared to414operated patients who received thyroid hormone alone[27].However,on closer scrutiny of the data,in only33patients was RAI given merely to ablate residual thyroid tissue.The majority of the patients had either residual neck nodal disease after primary surgery or lung metastases.Yet,on the basis of the encouraging results reported in these33 patients,postoperative management for thousands of PTC patients treated in the USA during the late1970s was forever changed[1],leading to a dramatic upsurge in the number of patients treated with RRA(Fig.2).In1981,Mazzaferri reported no improvement in recurrence rates after RAI in153patients with small (<1.5cm)primary tumors[28].His1987report[29] showed signiﬁcant differences in recurrence rates between those treated with RRA and thyroxine(9%) when compared to thyroxine only(17%).He reported in 1994that138of his Ohio State University(OSU)stage2 (intermediate-risk)or3(high-risk)patients with FCDC, treated by RRA,had a reduction in recurrence rates,when compared to patients treated with surgery and T4only (30-year rates of16%versus38%),and had not one cancer-related death after RRA,signiﬁcantly less than the 8%mortality rate seen in802patients not given RRA [30].However,in only138of the350patients reported as treated with RAI,could this treatment be classiﬁed properly as remnant ablation[3].These patients were combined for recurrence data,but the138RRA patients were analyzed separately for mortality.In1997,Mazzaferri further reported on151patients with FCDC,who had received RRA,and compared them to755who received thyroid hormone alone,and98who were given no postoperative therapy.All1,004patients had no apparent residual tumor after surgery.He reported that RRA‘‘is effective in reducing recurrence of FCDC in patients of all ages and reduces the risk of death from thyroid carcinoma in patients>age40at the time of diagnosis.’’This effect was not apparent in patients with isolated tumors smaller than 1.5cm with no nodal metastases or extrathyroidal invasion[31].He most recently reported on230FCDC patients who had received RRA,and found RRA was an independent variable that reduced cancer recurrence and death[32]. DeGroot et al.from the University of Chicago merely found a non-signiﬁcant trend towards reduced recurrence for patients with tumors more than1cm in size,either conﬁned to the thyroid or ing a Cox model,they were unable to conﬁrm any survival advantage for patients who received ing a chi square test,which is less rigorous,(since it only considers ﬁnal outcome and does not factor in duration of observation),they found that patients with>1cm intrathyroidal or node-positive tumors had a signiﬁcantly reduced risk of recurrence and death,if treated with RRA [33].Samaan and colleagues have also reported that RAI therapy is the most powerful prognostic indicator for increased disease-free interval and an important predictor of CSM[34].A group from UCSF also reported improved recurrence rates after RRA,but could not demonstrate improved CSM rates in patients with pTNM stage greater than T1N0M0[35].By contrast,Simpson and his colleagues from Toronto in1988found no signiﬁcant difference in recurrence rates or long-term cause-speciﬁc survival between patients who received RRA and those who did not,provided that the patients lacked microscopic or gross residual disease after surgical therapy[36].Schlumberger and colleagues at the Institut Gustave-Roussy found similar results[37]. Sanders and Cady also reported from the Lahey Clinic that RAI therapy did not signiﬁcantly improve survival in their AMES low-risk or high-risk FCDC patients[38].A number of other studies published in the1990s have also failed to conﬁrm a survival beneﬁt for patients treated with adjuvant RAI[3,39].Overall,the presently available retrospective data describing the efﬁcacy of RRA in PTC,especially in low-risk prognostic groups,is not convincing.Even a meta-analysis published in2004by Sawka and collea-gues from Canada[40],attempting to deﬁne from currently published reports the effectiveness(or not) of RRA for well-differentiated FCDC,concluded that ‘‘the effectiveness of RAI ablation in decreasing recurrence and possible mortality in low-risk patientsFig.2.Changing frequency of remnant ablation at Mayo Clinic during1970–2000in1,423PTC patients,without initial distant metastases,who underwent RRA within6months of potentially curative bilateral resection.694Haywith well-differentiated thyroid carcinoma,although suspected,cannot be deﬁnitively veriﬁed by summarizing the current body of observational patient data.’’Data from1990to2002Mayo-derived PTC studies certainly do not lend support to an enthusiasm for routine RRA in most patients with FCDC.In1990,it was reported that,of946Mayo patients similar in stage to Mazzaferri1987reported patients,220had received RRA within6months of bilateral potentially curative surgery.The recurrence rate was9.6%after surgery alone and13.3%in those who were ablated(P¼0.06).CSM rates at10years were insigniﬁcantly different at2%for the surgery alone group and3%for the ablated patients [1].Both groups received similar T4therapy and were of similar age(mean age43vs.41).In1997,Grebe and Hay reported that439ablated OSU stages2or3FCDC patients,having their initial treatment at Mayo,had comparable recurrence(17%vs.19%;P¼0.89)and CSM rates(5.9%vs.7.8%;P¼0.43),when compared to 1,103matched patients treated with only surgery and T4 [3].These results markedly disagreed with the results of Mazzaferri1987PTC report[29]and his1994FCDC report[30].It is very probable that the Mayo recurrence rates,which are considerably lower than those reported by other institutions,may be related to the extent and completeness of surgical excision typically performed at the Mayo Clinic[11–13].Additionally,Mayo authors[41]have shown that in papillary thyroid microcarcinoma(tumor size1cm or less),45ablated node-positive patients did not have signiﬁcantly fewer locoregional recurrences than108 non-ablated node-positive cases,the10-year rates being 9%and12%,respectively(P¼0.99).Also,in1992it was reported to the Endocrine Society that92ablated node-positive PTC patients with small tumors(1.5cm or less)had near-identical locoregional recurrence rates (P¼0.59)to194non-ablated cases[42].More recently, we reported identical recurrence and cause-speciﬁc mortality rates in371ablated AMES low-risk PTC cases and in1,267non-ablated cases[43].In2002we presented to the Society of Nuclear Medicine the results of a study of1,205PTC patients with primary tumors smaller than16mm diameter(mean age45years,median tumor size1cm),consecutively treated at Mayo during1940–2000,and followed for up to56years,median14years.After bilateral lobar resection(BLR),the risks of local or distant spread were not decreased by RRA,and the227ablated patients actually had higher rates of nodal recurrence(NR)than the833non-ablated(P<0.001).When NR rates were studied in the367node-positive patients,the20-year rate of15%after RRA and BLR was insigniﬁcantly different (P¼0.23)from the13%seen after only BLR.For node-negative patients treated by BLR,the20-year NR rate of 1%was not improved by RRA.We concluded that routine RRA,after BLR with apparently complete tumor excision,is no longer justiﬁable in the management of patients who present with small(<16mm diameter)PTC [44].It should also be recognized that RRA has the potential for signiﬁcant side effects.Short-term side effects include radiation thyroiditis(up to70%),sialoadenitis(up to 10%)which may become chronic,odynophagia,herpes zoster,leukopenia,endocrine and reproductive testicular and ovarian failure(mostly reversible),and radiation cystitis.Long-term carcinogenic risks may theoretically include leukemia,stomach,breast,and bladder cancer [3].Aldinger and associates from M.D.Anderson in 1978reported an incidence of undifferentiated thyroid cancer in4%of243patients treated with RAI[45].More recent concerns have been raised in both Europe and the United States regarding the possibility of RAI-treated patients later developing radiation-induced second malig-nancies,potentially resulting in increased overall non-thyroid cancer-related mortality[46–48].Another addi-tional consideration,particularly in an under-insured young PTC patient,could be that theﬁnancial cost and inconvenience may also outweigh any potential beneﬁt in a low-risk patient.CHALLENGES POSED IN THE POSTOPMANAGEMENT OF LOW-RISK PTC Consider the example of a25-year-old female presenting in the postpartum period with a 1.5cm palpable nodule in her right thyroid lobe.Aﬁne needle aspiration biopsy reveals cells that are highly suspicious for a PTC.A preoperative ultrasound scan reveals no suspicious lateral adenopathy,but does show tiny microcalciﬁed hypervascular nodules(3–6mm)in the left lobe,as well as a second smaller(7mm)non-palpable suspicious nodule within the right lobe.Neck exploration is advised.A near-total thyroidectomy and central compartment exploration is performed.Careful examina-tion of the thyroid and the level VI nodes reveals a bilateral multicentric histologic grade1PTC,which has involved two ofﬁve removed right central nodes.There was at surgery no evidence of extrathyroidal invasion of adjacent tissues,and tumor excision was complete,with no evidence of gross residual disease at the end of the surgical procedure.The patient is at the time of surgery both clinically and biochemically euthyroid,with a sensitive TSH of1.5mU/L,and a preoperative basal serum thyroglobulin of22ng/ml.The patient recognizes that she will have to take thyroid hormone daily for the rest of her life.She is prepared to put up with that minor hardship,and also is willing to be followed annually by a local endocrinologist Selective Use of Postop Radioiodine695in future years.She has,however,signiﬁcant misgivings about being given a dose of RAI for postoperative remnant ablation.In counseling this young woman,what data can a clinician turn to,in an attempt to allow her to make a proper decision about adjunctive RAI?She wants to know what will be her likely outcome,and whether the proposed RRA can really reduce her chance of dying from PTC or having her cancer recur in future years. Before providing advice to such a young woman with low-risk PTC,it might be relevant to give consideration to the likely‘‘natural history’’of her operated disease. This patient with PTC is25years old(<45years)and has no evidence of distant spread to our knowledge.She has a 1.5cm(T1)tumor and has evidence of regional nodal involvement(N1)in the central compartment(level VI). Her tumor does not exhibit local(extra-thyroid)invasion, and the tumor was apparently completely excised,with negative postoperative margins obtained.Her pTNM stage would be stage I(T1N1aMx)by the most recent AJCC classiﬁcation[49].By the criteria of AGES, AMES,and MACIS[50],she would be classiﬁed with an AGES score of<4,as an AMES low-risk category,and with a MACIS score of<6.It would be predicted that she would likely enjoy a99%20-year cause-speciﬁc survival from her PTC[1],and one might estimate that her chance of having a recurrent neck node discovered within20years of primary surgery would approximate 20%[51].Conventionally,she would be treated post-operatively with thyroid hormone suppressive therapy. The mainstay of her postoperative imaging over the years would likely be high-resolution ultrasound examination of her neck[52].Any recurrent tumor would likely arise in the neck,particularly on the side of her dominant nodule,perhaps related to the already known involvement of the right central compartment[1].The controversy in this case relates to the role of postoperative radioiodine remnant ablation(RRA)in preventing the development of loco regionally recurrent PTC[1,12].The concept of using remnant ablation with RAI to ‘complete a thyroidectomy’has existed since at least 1960,when Blahd and his colleagues at UCLA[20] described theirﬁrst decade’s experience with radio-isotope therapy and concluded that‘‘a realistic appraisal of the I-131treatment of thyroid cancer is extremely difﬁcult.The unfortunate muddling of therapeutic modalities and the remarkable longevity of many of these patients for the most part frustrates any forthright analysis.’’By1984,Beierwaltes from Michigan stated, based on their institutional experience of ablating511 patients with I-131,that‘‘there is no question today that we should ablate normal thyroid tissue as a part of the treatment of well-differentiated thyroid cancer’’[53]. By contrast,Gorman from Mayo Clinic in1983 emphasized that‘‘numerous studies support the use of radioiodine in the treatment of metastatic disease;but extrapolation to the practice of remnant ablation does not follow’’[54].After he demonstrated that,in patients with PTC,ablative therapy directed to postsurgical remnants ‘‘reduced visible I-131uptake to zero or nearly zero,but did not protect against tumor recurrence,’’he described the practice of RRA as‘‘the questionable pursuit of an ill-deﬁned goal’’[54].In the same issue of that journal, Sisson[4]from Ann Arbor observed that‘‘scintigrams have come to be worshiped as portents and as arbiters of proper treatment.’’From a review of the then available literature,which he described as‘‘a statistical labyrinth,’’he concluded that‘‘the aggregate of evidence does not convincingly demonstrate that ablation of small rem-nants—and especially those remote from the primary tumor—lowers the rate of recurrent cancer.Bearing these concepts in mind,each physician must decide from incomplete knowledge whether to use I-131as a radio-active eraser.’’Sisson proposed[4]in1983that‘‘to ablate or not to ablate is a question that will haunt us for some time to come.’’Even a recently published meta-analysis could notﬁnd convincing evidence for routine RRA in low-risk PTC and suggested that only a full-scale prospective controlled trial would truly establish answers to Sisson haunting question[40].If one were to design a prospective controlled trial to evaluate the role of RRA,one would wish to exclude patients with initial distant metastases and those who had undergone incomplete surgical resection of primary tumor,that is,restrict entry to patients undergoing potentially curative surgery.One would wish the patients to be matched for age,sex,extent of initial disease,and histology.Ideally,both groups should have a standard primary operation,preferably near-total(NT)or total thyroidectomy(TT),performed by specialist surgeons. To qualify as ablative therapy,the RAI would have to be administered for uptake conﬁned to the thyroid bed soon after the operation,typically within3–6months.Those patients,who would be randomly allocated to the surgery-only group,should be treated identically with regards to thyroxine suppressive therapy and followed in a similar manner to the ablated group by the same group of physicians.Follow-up data would require scrupulous evaluation with multivariate analyses.Obviously,such a prospective trial has not yet been planned.Indeed,Wong and colleagues[55]have suggested that for45-year-old women‘‘each arm of the trial would require nearly4,000 patients to detect a10%reduction in mortality after 25years...If one in every ten patients was enrolled in such a study,enrollment would take10years,and results would be available after35years.’’A more recent Dutch study would suggest that the number of patients needed to show a30%reduction in disease recurrence would be less than600[56].696HayIn the absence of such prospective data,the best available published data relates to retrospective studies of operated patients,who have comparable risk factors at presentation.The Mayo-derived AGES [57],and MACIS classiﬁcations [3,8]and Cady AMES risk-group cate-gories [7]have,in our opinion,allowed us to make some conclusions in PTC patient cohorts about the impact of initial extent of surgical resection in outcome results.In an attempt to quantify the inﬂuence of RRA on outcome after adequate initial surgery,we recently performed analyses on 1,163MACIS low-risk (scores <6)patients,who had undergone NT or TT during 1970–2000for tumors conﬁned to the neck and completely excised at initial neck exploration.These 1,163patients were operated in a standard manner by a small group of specialized Mayo surgeons,who had recognized exper-tise in endocrine surgery.The preoperative investigations and the postoperative care were provided by Mayo staff endocrinologists,who also prescribed and monitored the patients’postoperative thyroxine therapy [12].During 1970–2000,875PTC patients at Mayo-Rochester underwent initial NT,while 502had TT.Of these,848(97%)of the NT group and 472(94%)of the TT group had no distant spread at presentation and had complete tumor excision at initial surgery.Of these 1,320patients in the potentially curable NT/TT group,1,163(88%)were at presentation classiﬁed as having MACIS scores of <6.Four hundred ninety eight (43%)of these low-risk patients had RRA within 6months of the initial surgery.Those who received RRA were more likely to have had positive neck nodes at presentation (P <0.001).Of 636node-negative patients,195(31%)received RRA.However,of 527node-positive patients,303(57%)were ablated.Looking carefully at the 1,163MACIS <6PTC patients undergoing NT/TT at Mayo-Rochester,the majority (57%)had only surgery,but 498(43%)had RRA within 6postoperative months.At 20postoperative years the cause-speciﬁc mortality (CSM)rate for the surgery alone patients was 0.4%,and for the NT/TT and RRA group,it was insigniﬁcantly different at 0.6%(P ¼0.64).At 20years the tumor recurrence (TR)rate was actually signiﬁcantly higher in the ablated group (14%vs.9%:P ¼0.008),likely reﬂecting the tendency to more readily ablate node-positive patients.When the patients were divided into node-negative and node-positive groups,there were no statistically signiﬁ-cant differences in outcome (CSM and TR)between those having surgery alone and those who also received postoperative RRA (Table I).Interestingly,there were no deaths from PTC in the 636node-negative cases and only 2in the node-positive group.For the node–negative patients (Fig.3),the 20-year TR rates were 3.4%after surgery alone and 4.3%after surgery and RRA (P ¼0.80).For the node-positive group,who clearly had much higher TR rates,the CSM rates at 20years were 1.2%after surgery alone and 0.9%after RRA (P ¼0.99).The 20-year TR rates (Fig.4)only differed by 0.4%,being 19.5%for surgery alone and 19.9%for surgery and RRA (P ¼0.66).Thus,we have concluded that RRA did not signiﬁcantly improve the outcome (either CSM or TR)in low-risk (MACIS <6)patients previously treated with initial NT or TT.TABLE ck of Inﬂuence of RRA on Outcome in 1,163MACIS Low-Risk (Scores <6)Patients (Without Distant Metastases)Treated During 1970–2000at Mayo by Near-Total (NT)or Total Thyroidectomy (TT)Low-risk (MACIS <6)1970–200020-year mortality20-year recurrence NT/T alone NT/TT and RRANT/T alone NT/TT and RRAAll patients (1,163)0.4%0.6%8.7%13.6%P -valueP ¼0.64P ¼0.008Node-negative (636)0%0%3.4%4.3%P -valueN/AP ¼0.80Node-positive (527) 1.2%0.9%19.5%19.9%P -valueP ¼0.99P ¼0.66Fig.3.Survival to ﬁrst tumor recurrence during 20postoperative years in 636node-negative MACIS low-risk (scores <6)patients treated during 1970–2000.All 636initially underwent either near-total or total thyroidectomy;195(31%)additionally had RRA performed.Selective Use of Postop Radioiodine 697。

Loss of 1p, 19q, and 10q heterozygosity prospectively predicts prognosis of oligodendroglial tumors

Loss of 1p,19q,and 10q heterozygosity prospectively predicts prognosis of oligodendroglial tumors—towards individualized tumor treatment?Carole Ramirez,Clive Bowman,Claude-Alain Maurage,Franc ¸ois Dubois,Serge Blond,Nicole Porchet,and Fabienne EscandeNeuro-oncology and Neurosurgery Department,R.Salengro Hospital (C.R.,F.D.,S.B.),Neuropathology Department,Biology and Pathology Center (C.-A.M.),Biochemistry and Molecular Biology Department,Genetic Research,Biology and Pathology Center,Lille University Medical Center,Lille,France (N.P.,F.E.);Jean-Pierre Aubert Research Center,INSERM U837,Place de Verdun,Lille,France (C.R.,N.P.);School of Biological Sciences,The University of Reading,Whiteknights,Reading,United Kingdom (C.B.)The purpose of this study was to determine whether chromosome 10q loss is a predictor of tumor aggressive-ness and poor clinical outcome in patients with oligo-dendroglial tumors alone or together with loss of heterozygosity (LOH)on chromosomes 1p and 19q.A microsatellite analysis was performed on sections from 130patients with grade II and grade III oligodendroglial tumors to assess the allelic status of chromosomes 1p,19q,and 10q,plus detailed clinical and radiological information was taken prospectively.Median age at diagnosis was 45.5years.Seventy-eight patients had disease progression after initial therapy;median progression-free survival (PFS)was 27.5months.Age <47years,postoperative Karnofsky performance score >65,no contrast enhancement on MRI,grade II,and complete removal on surgery were signiﬁcantly corre-lated with a better PFS.Median overall survival (OS)was 40.5months.Pure oligodendroglioma and temozo-lomide chemotherapy were correlated with better OS.10q LOH was correlated with anaplastic grade and 1p19q LOH correlated with pure oligodendroglioma.There was a signiﬁcant association between LOH status and the tumors’response to chemotherapy:92.3%with 1p19q LOH,83.3%without allelic losses,50%with 1p19q10q LOH,and 14.5%with 10q LOH.Patients with 10q LOH alone had PFS of 6months and a 3-year survival rate of 1%,when com-pared with 36months and 85%,respectively,in patients with 1p19q LOH but without 10q LOH.1p loss was correlated with better PFS (P <.005)and OS (P 5.0007),whereas 10q loss was correlated with decreased PFS (P <.0001)and OS (P <.0001).10q LOH predicted a survival disadvantage in patients with oligodendroglial tumors irrespective of 1p /19q LOH status.Keywords:chemosensitivity,gliomas,loss of heterozygosity,prognosis,prospective study.Gliomas are a part of a wide and heterogeneous tumor type that accounts for approximately half of the new cases of primary brain tumorsdiagnosed annually in adults.At the present time,a his-tological classiﬁcation system is the standard for deter-mining glioma prognosis and is still essential before administering therapies.1The most frequently used classiﬁcation for pathological diagnosis is the WHO classiﬁcation.2However,there are signiﬁcant interobser-ver disparities in these classiﬁcations and gradings.3Gliomas are a heterogeneous entity.The clinical course and response to treatment are highly variable.The ﬁve-year survival rates for gliomas are reported to range from 2%to 75%.4,5On average,prognosis is largely inﬂuenced by the histological classiﬁcation,but patients’variability within each grade and type remains clinically signiﬁcant.It is also likely that varia-bility in neuropathologists’assessments accounts for some of this within-grade and within-type variability.Corresponding Author:Carole Ramirez,MD,Service de Neurochirurgie,Ho ˆpital Roger Salengro,CHRU de Lille,rue Emile Laine,F-59037Lille Cedex,France (c-ramirez@chru-lille.fr).Received July 8,2009;accepted October 14,2009.Neuro-Oncology 12(5):490–499,2010.doi:10.1093/neuonc /nop071NEURO-ONCOLOGY#TheAuthor(s)2010.Published by Oxford University Press on behalf of the Society for Neuro-Oncology.All rights reserved.For permissions,please e-mail:journals.permissions@.This within-group variability has prompted searches for additional prognostic factors,such as other clinical and molecular prognostic markers.6Even for the same histological type,gliomas show a variety of molecular genetic alterations.7,8It is reported that genetic proﬁles may help classify gliomas according to their response to chemotherapy and their risk of recurrence.9,10This new knowledge adds to the complexity of gliomas and prompts the need for developing novel treatment strat-egies.However,these genetic alterations are not found in all gliomas and are not strictly correlated with tumor type.Hence,despite its importance being ques-tioned,the relatively easy to perform and inexpensive histopathological diagnosis remains widely used.This clinical,histopathological,biomolecular,and genetic variability is challenging.The decision making and prognosis for an individual patient is difﬁcult in the absence of a sensitive and speciﬁc predictive model. Therefore,further research is needed.The discovery of new predictors,even if applicable only to a subset of patients,will help decision making.It is more likely that they will be part of more complex multivariate models,combining and investigating the correlation between clinical,histopathological,biomolecular,and genetic variables.The hope is that these multivariate models will lead ultimately to better classiﬁcations, decision trees and patient care.Various molecular techniques,including mutation analysis,allelotyping,in situ hybridization,comparative genomic hybridization,and gene-expression proﬁling have been used to study gliomas.11These studies have shown that gliomas result from the accumulation of several distinct chromosomal alterations such as loss of heterozygosity(LOH)on the short arm of chromosome 1(1p),the long arm of chromosome19(19q),and the long arm of chromosome10(10q).These acquired genomic alterations in tumor cells have an important role in formulating the prognosis of patients with gliomas,in addition to the histological classiﬁcation, because some correlate with the clinical outcome. Established indicators of the favorable outcome of oligo-dendroglial tumors include LOH on chromosomes1p and19q,which may indicate a loss of function of as yet unknown tumor-suppressor genes contained in those regions.Such alterations are strongly associated with better response to nonsurgical treatments and longer survival times,and continue to provide important prognostic information.12–15Conversely,deletion of chromosome10q has been shown to correlate with an aggressive behavior in gliomas,although this chromoso-mal alteration is less frequently found in oligodendro-glial tumors than in astrocytomas.16,17The presence of LOH on1p and19q does not ensure a completely accu-rate prognosis grouping,because all patients reported with this codeletion do not have better response to non-surgical treatments and longer survival times.This observation is critical for the precise prognosis of an individual patient.The reﬁnement of prognosis with the use of the analysis of LOH on10q in patients with or without1p19q codeletion provides the opportunity for a clinical trial that would evaluate the beneﬁt of the identiﬁcation of a subgroup of patients whose gliomas are estimated to be at high risk for recurrence.Thus,in this study,we assessed the allelic status of chromosomes1p,19q,and10q in a cohort of patients with oligodendrogliomas and mixed oligoastrocytomas by microsatellite analysis on formalin-ﬁxed parafﬁn-embedded sections.We correlated the molecular results with the clinical data,especially to determine the impact of each genotype on survival and the response to chemotherapy and/or radiotherapy.To this end,we wished to investigate whether chromosome10q loss is a predictor of tumor aggressiveness and poor clinical outcome in patients with oligodendroglial tumors;to use it to predict the individual risk of disease pro-gression;and to improve the selection of appropriate patients individually,for managing new strategies and choices of treatments.Provision of optimal care for an individual patient requires prudence to achieve the best overall survival(OS)and quality of life.Patients and MethodsClinical DataThis work is based on the prospective analysis of clinical and molecular information on patients treated in the Neurosurgery Department of Lille University Medical Center for primary brain glioma,from January2003 to December2005.Data were collected from patients aged18or older who presented for initial consultation or routine follow-up.The selection of the patients was limited by the pathological diagnosis of a low-grade or an anaplastic cerebral supratentorial glioma—grade II and grade III,according to the WHO classiﬁcation—including oligodendroglioma and oligoastrocytoma, and the availability of paired blood and tumor tissue for molecular analysis.Patients were excluded from the analysis if they had associated cancer,familial history of gliomas,or had received preoperative radiation therapy or chemotherapy.Patients had detailed clinical information taken at diagnosis and during follow-up.The following par-ameters were determined:gender,ﬁrst symptom,time interval between the time of appearance of theﬁrst symptoms and the date of diagnosis,initial tumor location,tumor volume,MRI contrast enhancement, time interval between the time of diagnosis and the date of the initial surgery,type of surgery treatment (biopsies,partial resection,complete resection),pre-and postoperative Karnofsky performance score(KPS), type of adjuvant treatment(radiotherapy,type of chemotherapy),radiological response to adjuvant treat-ment,time of the recurrent tumor growth(progression-free survival[PFS]),and patient status at the last follow-up(dead or alive).Postoperative imaging studies,all done within the3days after surgery,were compared with MRIs that were available during the follow-up of the patient.The radiological response to radiotherapy or chemotherapy was evaluated over at least3cycles.A25%change in volume was necessaryRamirez et al.:Loss of1p,19q,and10q heterozygosity predicts prognosis of oligodendroglial tumorsNEURO-ONCOLOGY†M A Y2010491for the recognition of progression or regression. Follow-upﬁndings were conﬁrmed in all patients as of January2008.There were no missing data.No patient was lost to follow-up.NeuropathologyImmediately after surgical removal,tumor samples were placed in tissue-culture media and shipped to a central reference laboratory for studies of tumor biology. Surgical specimens were saved as formalin-ﬁxed and parafﬁn-embedded for histopathological examination. Samples of tumors were diagnosed by a neuropatholo-gist and were graded according to WHO classiﬁcation. Parafﬁn-embedded sections from tumors that were com-posed of at least90%tumor cells were selected for the molecular analysis.Molecular AnalysisTumor DNA was isolated from30-m m parafﬁn-embedded sections by overnight proteinase K digestion following xylene/ethanol deparafﬁnization and extracted using the QIAamp DNA Mini w kit (Qiagen)or NucleoSpin Tissue kit(Macherey-Nagel) according to the manufacturer’s instructions. Corresponding constitutional DNA was extracted from peripheral blood leukocyte with the use of the QIAmp DNA Blood Maxi kit(Qiagen).LOH on chromosomes1p,19q,and10q was detected by microsatellite analysis on blood and tumor DNA, respectively,using the following20polymorphic markers:D1S468,D1S214,D1S1612,D1S2736, D1S1597(located on1p36.32–36.21);GATA129H04 (located on1p34.2);D1S1728(located on1p31.1);D19S245,D19S178,D19S112,D19S412,D19S606, D19S596,D19S246(located on19q13.11–13.33); D10S1649(located on10p14);D10S1790(located on 10q21.1);D10S1765(located on10q23.31);D10S1692 (located on10q24.32);and D10S1483,D10S212 (located on10q26.13–26.3).These microsatellite markers span the regions of chromosomes1p and19q that are commonly lost in oligodendroglial tumors—between1p36.32and1p31.1on chromosome1p and between19q13.11and19q13.13on chromosome19q—or on the entire long arm of chromosome10q near the genes of interest(Fig.1and Table1).The primer sequences of all markers were obtained from the Genome Database ().The order of microsatellite markers on the chromosomes was according to relevant data on the Web sites at Ensemble() and at GeneLoc().Microsatellite markers were selected based on amplicon size and hetero-zygosity score.One of each speciﬁc primer pairs was labelled using3differentﬂuorochromes:6-FAM(blue), NED(yellow),and HEX(green)(Applied Biosystems) for use in a single-run analysis.Six multiplex PCR ampliﬁ-cations were performed using Qiagen Multiplex PCR kit (Qiagen).The reaction mixture(50m L)contained25m L of2ÂMultiplex Master Mix,5m L of each sense and anti-sense primer(2pmol/m L),and1m L genomic DNA (100ng/m L)or5m L tumor DNA.Multiplex PCR A con-sisted of the microsatellite markers D1S468,D1S214, D1S1612,D1S2736;multiplex PCR B consisted of GATA129H04,D1S1728,D19S245,D19S112;multi-plex PCR C consisted of D19S606,D19S596,D19S246; multiplex PCR D consisted of D19S178,D19S412, D1S1597;multiplex PCR E consisted of D10S212, D10S1692,D10S1765;and multiplex PCR F consisted of D10S1649,D10S1790,and D10S1483.PCR cycles were performed using a GeneAmp w PCR system9700 Fig.1.Chromosomal location of the33polymorphic markers used.Ramirez et al.:Loss of1p,19q,and10q heterozygosity predicts prognosis of oligodendroglial tumors492NEURO-ONCOLOGY†M A Y2010(Applied Biosystems)as follows:initial denaturation step at958C for10minutes,followed by5cycles with dena-turation at958C for20seconds,annealing at608C for1 minute30seconds with218C at each cycle,and extension at728C for1minute and by30cycles with denaturation at 958C for20seconds,annealing at558C for1minute 30seconds,and extension at728C for1minute.The ﬁnal extension step was for30minutes at608C.PCR pro-ducts were run on an automatic sequencer ABI prism Model377XL w or3100-Avent Genetic Analyzer (Applied Biosystems).Data were collected automatically during electrophoresis and then analysed with the Gene Scan software(Applied Biosystems).For heterozygous samples,a reduction of at least 50%(allelic imbalance factor,IF,of0.50)in the peak area of one allele in the tumor(normalized against the retained allele)was used to score LOH.In each case,the IF was determined by calculating the ratio of alleles for both the constitutional(C)and the tumor (T)sample,and then the tumor ratio was divided by the constitutional ratio:R¼½T1 =½T2½C1 =½C2ÁIf the value obtained was greater than1.00,the reci-procal1/R was used.Thirteen additional markers located on chromosome1p or19q were also analyzed when the LOH status need to be conﬁrmed:D1S243 (located on1p36.33),D1S2845,and D1S2660 (located on1p36.32);D1S2795,D1S2870,and D1S2663(located on1p36.31);D1S548(located on 1p36.23);D1S450,D1S1151,D1S2667,andTable1.Data on polymorphic microsatellite markers usedMarkers Chromosomal location Chromosomal location(base pair)Percentage of heterozygosity Allele size Chromosome1D1S243p36.332129134–212929586142–170 D1S468p36.32350819–370834275173–191 D1S2660p36.324704510–470477078253–261 D1S2795p36.315499155–549937875214–224 D1S2870p36.316212351–621256075190–212 D1S214p36.316884605–688480079120–142 D1S2663p36.317180181–718037585183–205 D1S548p36.237365426–736558867148–172 D1S1612p36.238040572–80406848394–130 D1S450p36.229508007–950826981243–367 D1S2736p36.2210615664–1061578373122–132 D1S1151p36.2211387148–1138742092263–332 D1S2667p36.2211409625–1140989482246–272 D1S2740p36.2211843587–118436766580–104 D1S1597p36.2113656774–1365694366159–179 GATA29A05p36.1317428904–1762922271179–211 GATA129H04p34.241499079–4149929388204–256 D1S1728p31.181610619–8181077868158–174 D1S2707q23.2158339075–15833922382137–159 Chromosome19D19S898p13.1118334781–1833496082178–200 D19S245q13.1138789997–3879020168195–211 D19S219q13.3250685577–5068575077160–190 D19S112q13.3251070821–5107095086120 D19S412q13.3251702813–517029218089–113 D19S606q13.3252665381–5266555881172–190 D19S596q13.3353942842–5394305453213–221 D19S246q13.3355647457–5564766284185–229 Chromosome10D10S1649p149460072–946021184126–150 D10S1790q21.154875447–5487563183179–201 D10S1765q23.3189591521–8959170083166–184 D10S1692q24.32104578855–10457905388182–211 D10S1483q26.131********–12327372782130–158 D10S212q26.3134299591–13429977970189–201Ramirez et al.:Loss of1p,19q,and10q heterozygosity predicts prognosis of oligodendroglial tumorsNEURO-ONCOLOGY†M A Y2010493D1S2740(located on1p36.22);GATA29A05(located on1p36.13);and D19S219(located on19p13.32) (Fig.1and Table1).We determined chromosome losses as the complete or partial loss of the1p,19q,and10q.During the assess-ment of allelic status,investigators were blinded to the characteristics of the patients and to follow-up data. Statistical MethodsThe statistical endpoints in our analyses were PFS,OS, and response to chemotherapy.Events for the PFS analy-sis were deﬁned as relapse or disease progression.The time to an event for the relapse was calculated as the date of surgery to the time of theﬁrst relapse or the time of last contact with the patient if no event occurred.The time to an event for the OS analysis was calculated as the date of surgery until the time of death or the time of last contact if the patient was alive. Data on survival were censored if patients had died from potentially other causes.Note that no patient was lost to follow-up and that all patients progressed before dying.Also note that these deﬁnitions of PFS and OS are taken from the time of surgery(ie the time of the therapeutic intervention)and not the time of diag-nosis as in conventional deﬁnitions of PFS and OS,as we are interested in understanding the interplay of LOH with the consequences of surgery for the patient.Two analysis approaches were taken:First,univariate analyses to evaluate the importance of each factor on its own,then a multivariate analysis in order to allow for any codependencies between factors.We calculated uni-variate hazard ratios with the proportional-hazards model.Tests of association were performed with the use of Fisher’s exact test for categorical data and Wilcoxon rank-sum test for continuous data.Survival curveswere constructed according to the methods of Kaplan and Meier and comparisons of the survival curves were performed with a two-sided log-rank test. Multivariate analyses were performed with the use of a Cox proportional-hazards regression model to identify variables that were independently predictive of outcome.All covariates were retained in the model to illustrate the lack of effect in the presence of other signiﬁ-cant factors.ResultsCharacteristics of the Patients and Correlationswith PrognosisOne hundred and forty-ﬁve patients were included pro-spectively at the time of their surgery into the molecular study.We removed15patients presenting with partial LOH on1p,19q,or10q due to the possible different prognosis reported in the literature.Table2lists the relevant demographic and clinical characteristics of the130patients whose gliomas were analyzed by micro-satellite analysis.Overall,116patients received adjuvant treatment:(i) postoperative radiotherapy followed by chemotherapy in25patients,(ii)postoperative chemotherapy alone in 18patients,(iii)postoperative radiotherapy alone in73 patients,and(iv)chemotherapy at tumor progression in26patients.Thirty patients received temozolomide and39patients received PCV(procarbazine,CCNU, vincristine)regimen as chemotherapy.Thirty-six of the 69chemotherapy-treated patients showed positive or stable radiological tumor responses.Relevant data concerning the ability to predict response to chemotherapy are listed in Table3.There was no difference in the frequency of the response to che-motherapy in each histological subgroup of gliomas(P¼.2),and between appearance or not for contrast enhance-ment on MRI(P¼.06).The time to start chemotherapy, immediately following radiotherapy,or when gliomas relapsed,was not associated with the response to che-motherapy(P¼.8).The duration of survival was inde-pendent of the timing of the introduction of chemotherapy;it was not that because the chemotherapy was introduced earlier,patients would survive longer.Of the tumors treated by chemotherapy,41%presented a positive response to the PCV regimen and66.7%were Table2.Clinical and molecular features in oligodendroglial tumors(130patients)Descriptive data ResultsClinical featuresMedian age at diagnosis,y(range)45.5(19–73.5) Number:male/female68/62Median preoperative KPS(range)90%(30%–100%) Median postoperative KPS(range)90%(50%–100%) Symptoms at diagnosisSeizure76(58.5%) Combination of neurological deﬁcitand epilepsy31(24%)Unusual headache11(8.5%)Raised intracranial pressure9(7%)No symptoms3(2%)MRI contrast enhancement(%)76(58%)SurgeryBiopsy57(44%)Partial removal41(31%)Total removal32(25%) HistopathologyGrade2oligodendroglioma28(22%)g64 Grade3oligodendroglioma36(28%) Grade2oligoastrocytoma24(18%)g66 Grade3oligoastrocytoma42(32%)Genomic featuresNo deletion46(25.5%)1p and/or19q LOH33(35.5%)10q LOH40(30.5%)1p,19q,and10q LOH11(8.5%) Abbreviations:KPS,Karnofsky performance status;LOH,loss of heterozygosity.Ramirez et al.:Loss of1p,19q,and10q heterozygosity predicts prognosis of oligodendroglial tumors 494NEURO-ONCOLOGY†M A Y2010clinically and radiologically improved by temozolomide.The result was not signiﬁcant (P ¼.51).In univariate analysis,the only signiﬁcant clinical factor relating to the response to chemotherapy was the postoperative KPS (P ¼.03).Data regarding the ability of the various clinical,radiological,and neuropathology factors to predict clini-cal outcome are reported in Tables 4(PFS)and 5(OS).The mean PFS for all patients was 27.5months.Fifty-two patients relapsed and 26patients had a continuous tumor progression despite various therapy strategies.At the time of analysis,mean survival was 40.5months,and 60patients (46%)had died.As expected,in univariate analysis,5variables studied had signiﬁcant prognostic value for OS and PFS.Age .47,postoperative KPS ,65,positive contrast enhance-ment,and grade 3tumors were associated with a signiﬁ-cantly higher risk of death or progression,whereas complete removal on surgery—conﬁrmed on postopera-tive MRI—was associated with a better prognosis.Table 4.Univariate analysis:correlation between analyzed data and progression-free survival DataCategories comparedMean PFS (m)P valueMean PFS period 27.5Clinical Sex Male vs female 28.6vs 23.1.6Age (y)47vs .4727.7vs 22.1.001Postoperative KPS (%) 65vs .65 4.7vs 29.5,.0001RadiologicalContrast enhancement No vs yes 32.8vs 22.3.0007Neuropathology Tumor type O vs OA 24vs 25.5.19Grade2vs 332.1vs 23.1.0037TreatmentQuality of surgery B vs PR vs CR 22.3vs 24vs 32.015PR vs CR 24vs 32.2Genomic data LOH 1p No LOH vs LOH 22.6vs 32.5,.0001LOH 19q No LOH vs LOH 24.1vs 30.4.0035LOH 10qNo LOH vs LOH 40.5vs 7.9,.0001Abbreviations:PFS,progression-free-survival;KPS,Karnofsky performance status;O,oligodendroglioma;OA,oligoastrocytoma;B,biopsy;PR,partial removal;CR,complete removal;LOH,loss of heterozygosity.Table 3.Correlations between analyzed data and response to chemotherapy Data Categories comparedPositive response,%P valueClinical SexMale vs female 55%vs 48%.6Age (y)47vs .4752%vs 49%.4Postoperative KPS (%) 65vs .6535%vs 65%.03RadiologicalContrast enhancement No vs yes 70%vs 45%.06Neuropathology Tumor type O vs OA 56%vs 48.5%.6Grade 2vs 368.5%vs 46%.1TreatmentDelay of chemotherapy Postoperative vs relapse 48%vs 54%.78Type of chemotherapy PCV vs TMZ 41%vs 66.7%.051Allelic status1p and 19q LOH 92.3%g,.0001vs no deletionvs 83.3%vs 1p,19q,and 10q LOH vs 50%vs 10q LOHvs 14.5%Abbreviations:PFS,progression-free survival;KPS,Karnofsky performance status;O,oligodendroglioma;OA,oligoastrocytoma;B,biopsy;PR,partial removal;CR,complete removal;PCV,procarbazine,CCNU,vincristine;TMZ,temozolomide;LOH,loss of heterozygosity.Ramirez et al.:Loss of 1p,19q,and 10q heterozygosity predicts prognosis of oligodendroglial tumorsNEURO-ONCOLOGY†M A Y 2010495Tumor histology and type of chemotherapy used were only signiﬁcant in the OS analysis.Assessment of the Allelic Status of Chromosomes 1p,19q,and 10qData regarding the genomic alterations analyzed in cohort of 130patients affected by oligodendroglial tumors are reported in Table 6.Thirty-three tumors (25.5%)showed combined losses of 1p and 19q.LOH on 10q,without deletions on chromosomes 1p19q,was identiﬁed in 40tumors (30.5%).Only 11tumors (8.5%)had LOH on 1p,19q,and 10q.Forty-six tumors (35.5%)had no LOH.Correlations of Allelic Status with ClinicalCharacteristics and Evaluation of the Prognostic Value of 10q LossLOH status was independent of the patient’s sex (P ¼.5)but correlated signiﬁcantly with patient’s age (P ¼.0009).At the tumor’s diagnosis,mean age was 39in the absence of LOH (median:36.5),45in 1p and 19q LOH (median:46),50in 10q LOH (median:52.5),and 54.5years old in 1p,19q,and 10q LOH (median:56.5).In our cohort of patients,10q LOH was associ-ated with anaplastic grade (P ¼.0023),whereas 1p and 19q LOH was mainly correlated with pure oligoden-droglial tumors whatever the grade (P ¼0.0015)(data not shown).As expected,the LOH status was an important factor for the tumor response to chemotherapy (P ,.0001)(Table 3).Sixty-nine patients received chemotherapy during the study.The clinical and radiological response to chemotherapy was 92.3%for tumors with 1p and 19q LOH,83.3%for tumors without allelic losses,50%for tumors with 1p,19q,and 10q LOH,and only 14.5%for those with 10q LOH alone.A univariate analysis of patients’outcomes showed that both 1p LOH and 19q LOH were highly associated with increases in both PFS (P ,.0001and P ¼.0035,respectively)and 3-year survival rate (P ¼.0002and P ¼.003,respectively).Analysis of the subgroup of cases showed that LOH on 10q was signiﬁcantly associ-ated with a decreased probability of PFS (P ,.0001)andTable 6.Genomic alterations by histology and grade of the tumors Genetic alterations O II O III OA II OA III Number of patients (%)1p and /or 19q LOH 9(7%)15(11.5%)3(2.5%)6(4.5%)33(25.5%)No deletion12(9%)5(4%)16(12.5%)13(10%)46(35.5%)1p,19q,and 10q LOH 1(0.75%)3(2.5%)1(0.75%)6(4.5%)11(8.5%)10q LOH 6(4.5%)13(10%)4(3%)17(13%)40(30.5%)Total28362442130Abbreviations:O II,oligodendroglioma grade II;O III,oligodendroglioma grade III;OA II,oligoastrocytoma grade II;OA III,oligoastrocytoma grade III;LOH,loss of heterozygosity.Table 5.Univariate analysis:correlation between analyzed data and overall survival Data Categories compared Overall 3-y survival rate (%)P valueClinical Sex Male vs female 58vs 51.56Age (y)47vs .4765vs 40.002Postoperative KPS (%) 65vs .650vs 60,.0001RadiologicalContrast enhancement No vs yes 70vs 42.5.0002Neuropathology Tumor type O vs OA 60vs 48.033Grade2vs 366vs 45.0009TreatmentQuality of surgery B vs PR vs CR 39vs 58vs 72.01PR vs CR 58vs 72.15Delay for chemotherapy Post-op vs relapse 42vs 25.5Type of chemotherapy PCV vs TMZ26.5vs 46.02Genomic data LOH 1p No LOH vs LOH 45.5vs 73.0002LOH 19q No LOH vs LOH 48vs 68.003LOH 10qNo LOH vs LOH86.5vs 3,.0001Abbreviations:OS,overall survival;KPS,Karnofsky performance status;O,oligodendroglioma;OA,oligoastrocytoma;B,biopsy;PR,partial removal;CR,complete removal;PCV,procarbazine,CCNU,vincristine;TMZ,temozolomide;LOH,loss of heterozygosity.Ramirez et al.:Loss of 1p,19q,and 10q heterozygosity predicts prognosis of oligodendroglial tumors496NEURO-ONCOLOGY†M A Y 2010。

肾脏在血糖调控中的作用

• 314 •中国糖尿病杂志2021 年4月第 29 卷第4期 Chin J Diabetes，April 2021，Vol. 29,No. 4肾脏在血糖调控中的作用刘倩伶李雪梅【提要】随着对D M 发病机制的深人研究，目前肾脏对血糖的调节作用逐渐受到关注。

生理状态，肾脏对葡萄糖代谢的调节包括糖异生产生葡萄糖、对葡萄糖的摄取和利用及近端小管钠-葡萄糖协同转运蛋白（SG LT1、SG L T 2)介导的葡萄糖重吸收，对维持血糖稳态起重要作用。

然而，在T 2D M 患者肾脏存在广泛的糖调节异常：空腹及餐后状态肾脏糖异生及肾脏对葡萄糖的摄取均增加，肾脏葡萄糖重吸收增加。

S G L T 2是近端小管介导葡萄糖重吸收最主要的转运体。

选择性的S G L T 2抑制剂已成为治疗T 2D M 患者的新一类降糖药，通过促进尿葡萄糖和钠排泄,S G L T 2抑制剂可降低血糖、血压。

同时可改善In s 分泌及敏感性，降低糖毒性，改善T 2D M 患者的血流动力学变化，减少心血管事件及延缓D K D 进展。

然而,其作为T 2D M 标准治疗的可行性及相关机制仍有待进一步研究。

本文对生理状态及T 2D M 状态肾脏对血糖的调控及S G L T 2抑制剂对机体的治疗效应进行综述。

【关键词】肾脏;糖尿病，2型；葡萄糖代谢异常;钠-葡萄糖协同转运蛋白2抑制剂doi ： 10. 3969/j. issn. 1006-6187. 2021. 04. 016The role of kidney in glucose homeostasis LIU Qianling , LI Xuemei. Department o f Nephrology , Peking Union Medical College Hospital，Beijing 100730，China Corresponding author: LI Xuemei ，Email:lixmpumch@ 126. com【Summary 】 With the deep research of the pathogenesis of diabetes mellitus，the role of kidney in glucose homeostasis attracts more and more attention. In physiological status, kidney regulation on glucose metabolism includes producing glucose through gluconeogenesis, using glucose as a metabolic fuel, and reabsorbing all filtered glucose through the sodium - glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule, which plays an important role in maintaining glucose homeostasis. However, handling of glucose by the kidney is widely altered in type 2 diabetes mellitus (T2D M ) ： renal gluconeogenesis and renal glucose uptake are increased in both the fasting and postprandial states, and renal glucose reabsorption is increased. The sodium glucose cotransporter SGLT2 in the early proximal tubule is the major pathway for renal glucose reabsorption. Specific SGLT2 inhibitors are being developed as a novel agent of controlling hyperglycaemia in T2DM. By promoting urinary glucose and sodium excretion, SGLT2 inhibitors lead to a reduction in plasma glucose and blood pressure levels. It also improves insulin secretion and sensitivity, ameliorates glucotoxicity and induces haemodynamic effects that lead to improved cardiovascular and renal outcomes in T2DM patients. However,the feasibility of its use as standard treatment for T2DM and its related mechanism still need to be further studied. In this review we examine the role of kidney in glucose homeostasis in the physiological status and T2DM and therapeutic significance through SGLT2 inhibitors.【Key words 】 Kidney ； Diabetes mellitus, type 2 ； Abnormal glucose metabolism ； SGLT2 inhibitor 目前肾脏在血糖调节中的作用越来越受到关注。

司美格鲁肽与达格列净分别联合二甲双胍治疗初诊肥胖2型糖尿病的效果比较

药物与临床DOI：10.16662/ki.1674-0742.2023.13.125司美格鲁肽与达格列净分别联合二甲双胍治疗初诊肥胖2型糖尿病的效果比较赵晨，陈婧，杨馥铭哈尔滨市第一医院内分泌科，黑龙江哈尔滨150010［摘要］目的比较司美格鲁肽与达格列净分别联合二甲双胍治疗初诊肥胖2型糖尿病的效果。

方法方便选取2021年3—12月哈尔滨市第一医院内分泌科收治的52例初诊肥胖2型糖尿病患者为研究对象，按照随机数表法分为司美格鲁肽组（Sem组）和达格列净组（Dap组），各26例。

Sem组患者采用司美格鲁肽联合二甲双胍治疗，Dap组患者采用达格列净联合二甲双胍治疗，12周后对比治疗前后空腹血糖（FPG）、餐后2 h血糖（2 hPG）、体质指数（BMI）、胰岛素抵抗指数（HOMA⁃IR）、收缩压（SBP）、舒张压(DBP)、糖化血红蛋白（HbA1c）及血糖达标率。

结果治疗后，两组患者的BMI、FPG、2 hPG、HbA1c、HOMA-IR、SBP、DBP均低于治疗前，差异有统计学意义（P<0.05）。

治疗后，Dap组患者的BMI（26.50±1.29）kg/m2、HOMA-IR（2.67±0.83）均高于Sem 组，SBP（115.35±10.59）mmHg、DBP（72.23±5.63）mmHg均低于Sem组，差异有统计学意义（t=2.100、2.287、2.234、3.453，P<0.05）。

Sem组血糖达标率（73.1%）与Dap组血糖达标率（92.3%）比较，差异无统计学意义（χ2=2.150，P=0.143）。

结论对于初诊肥胖的2型糖尿病患者，司美格鲁肽与达格列净分别联合二甲双胍降糖的效果相当。

司美格鲁肽联合二甲双胍在减重、改善胰岛β细胞功能方面的作用更明显，而达格列净联合二甲双胍在降压方面更有优势。

［关键词］司美格鲁肽；达格列净；初诊肥胖；2型糖尿病［中图分类号］R4 ［文献标识码］A ［文章编号］1674-0742（2023）05(a)-0125-04Comparison of the Effects of Semaglutide and Dapagliflozin in Combina⁃tion with Metformin for Primary Diagnosis of Obese Type 2 Diabetes Mel⁃litus RespectivelyZHAO Chen, CHEN Jing, YANG FumingDepartment of Endocrinology, Harbin First Hospital, Harbin, Heilongjiang Province, 150010 China[Abstract] Objective To compare the effects of semaglutide and dapagliflozin combined with metformin respectively in the treatment of primary obese type 2 diabetes mellitus. Methods Fifty two newly diagnosed obese type 2 diabetes patients admitted to the Department of Endocrinology of Harbin First Hospital from March to December 2021 were conveniently selected as the research objects. According to the random number table method, they were divided into smeglutide group (Sem group) and daggliptin group (Dap group), with 26 cases in each group. The Sem group patients were treated with Smeglutide combined with metformin, while the Dap group patients were treated with Daggliflozin combined with metformin. After 12 weeks, fasting blood glucose (FPG), 2-hour postprandial blood glucose (2 hPG), body mass index (BMI), insulin resistance index (HOMA-IR), systolic blood pressure (SBP), diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), and blood glucose compliance rate were compared before and after treatment.Results After treatment, the BMI, FPG, 2 hPG, HbA1c, HOMA-IR, SBP, and DBP of the two groups of patients were significantly lower than before treatment , the difference was statistically significant (P<0.05). The BMI (26.50±1.29) kg/m2and HOMA-IR (2.67±0.83) of patients in the Dap group were higher than those in the Sem group, while SBP[作者简介] 赵晨（1989-），女，硕士，主治医师，研究方向为糖尿病。

地诺孕素用于子宫内膜异位症保守术后维持治疗的Meta分析

地诺孕素用于子宫内膜异位症保守术后维持治疗的Meta 分析黄婷，黄高廷，杨国敏，梁梦姗，朱耀魁【摘要】目的：比较地诺孕素与其他治疗方法在预防腹腔镜下子宫内膜异位症（EMs ）保守术后复发的有效性及安全性，从而为临床上药物的选择提供参考依据。

方法：检索PubMed 、Embase 、Cochrane Library 、Web of Science 、Clini －、中国知网、万方及维普数据库自建库至2020年4月的相关文献和试验，检索的文献由两名评价人员独立筛选、质量评价以及数据提取，最终纳入的数据使用Revman 5.3进行Meta 分析。

结果：最终纳入10篇文献，共1740例患者。

Meta 分析结果显示，地诺孕素较期待治疗的病灶复发风险低（OR=0.11，95%CI ：0.07～0.19，P ＜0.00001），并能缓解EMs 相关疼痛；地诺孕素与促性腺激素释放激素激动剂（GnRHa ）治疗相比，病灶复发风险（OR=0.49，95%CI ：0.19～1.24，P=0.13）及疼痛缓解情况（P ＞0.05）差异无统计学意义，地诺孕素治疗后阴道出血（RR =13.11，95%CI ：5.02～34.21，P ＜0.00001）发生风险较高，潮热发生风险较低（RR =0.12，95%CI ：0.06~0.26，P ＜0.00001），差异有统计学意义，头痛（RR =3.49，95%CI ：0.99～12.25，P=0.05）发生风险较高，但差异无统计学意义；地诺孕素与左炔诺孕酮宫内缓释系统（LNG-IUS ）治疗相比，病灶复发风险差异无统计学意义（OR=0.46，95%CI ：0.50～1.04，P=0.06），地诺孕素能有效缓解EMs 相关疼痛（SMD =－0.46，95%CI ：－0.70～－0.22，P=0.0001），地诺孕素治疗后发生阴道出血（OR=0.38，95%CI ：0.18～0.81，P=0.01）、阴道分泌物增加（OR=0.03，95%CI ：0.00～0.48，P=0.01）及同房不适（OR=0.04，95%CI ：0.00～0.70，P=0.03）的风险相对较低；与米非司酮相比，地诺孕素能降低病灶复发风险（OR=0.41，95%CI ：0.18~0.96，P=0.04），且缓解疼痛的疗效相对较好（OR=21.00，95%CI ：2.65～166.45，P=0.004），地诺孕素发生潮热的风险较低（OR=0.11，95%CI ：0.01～0.89，P=0.04）。

如何对待疑似病人英语作文

如何对待疑似病人英语作文Handling Suspected Patients: A Comprehensive Approach。

In today's global landscape, especially with theongoing challenges posed by infectious diseases, dealingwith suspected cases requires a delicate balance of caution, empathy, and efficiency. As we navigate through uncertain times, it's crucial to adopt a systematic approach to manage suspected cases effectively. Here's how:1. Early Identification: Prompt identification of suspected cases is paramount. This involves recognizing symptoms commonly associated with the particular disease in question. Fever, cough, shortness of breath, fatigue, and body aches are typical indicators. Additionally, recent travel history or contact with confirmed cases should raise red flags.2. Isolation Protocol: Once a suspected case is identified, immediate isolation is necessary to preventpotential spread. Isolation facilities should be equipped with proper ventilation and protective gear for healthcare workers. The patient should be isolated in a designated area away from other patients and visitors.3. Communication and Education: Clear communication is essential to avoid panic and misinformation. Informing the suspected patient about the situation, necessary precautions, and the importance of isolation is crucial. Additionally, educating the public about symptoms, preventive measures, and when to seek medical help can help contain the spread.4. Testing and Diagnosis: Timely testing is vital to confirm or rule out the infection. Utilizing reliable diagnostic tests ensures accurate results. Rapid antigen tests or PCR tests are commonly used depending on availability and accuracy. However, while awaiting results, the suspected patient should continue to be isolated to prevent potential transmission.5. Contact Tracing: Identifying and monitoringindividuals who have been in close contact with the suspected case is imperative. Contact tracing helps breakthe chain of transmission by identifying potential secondary cases early on. These contacts should be advisedto self-isolate and monitor symptoms for a specified period.6. Medical Care and Support: Providing adequate medical care and support to suspected cases is essential for their well-being and recovery. Symptomatic treatment, such asfever management and respiratory support, should be administered as needed. Psychological support is alsocrucial to alleviate anxiety and stress associated with isolation and uncertainty.7. Follow-Up and Monitoring: Continuous monitoring of suspected cases is necessary to track their progress and detect any complications. Regular follow-up consultations with healthcare professionals ensure proper management and timely intervention if symptoms worsen.8. Discharge Protocol: Once the suspected case tests negative and symptoms resolve, a systematic dischargeprotocol should be followed. This involves ensuring the patient's fitness for discharge, providing guidance onpost-isolation precautions, and emphasizing the importanceof ongoing preventive measures.9. Data Sharing and Collaboration: Collaboration between healthcare facilities, public health authorities, and research institutions is vital for effective management of suspected cases. Sharing data on confirmed and suspected cases, as well as epidemiological information, facilitatesa coordinated response and informed decision-making.10. Preventive Measures: Finally, implementing preventive measures such as vaccination, hand hygiene,mask-wearing, and social distancing is crucial in reducing the risk of transmission and mitigating the impact of infectious diseases in the community.In conclusion, a comprehensive approach to handling suspected cases involves early identification, isolation, clear communication, testing, contact tracing, medical care, follow-up, discharge planning, collaboration, andpreventive measures. By adhering to these principles and protocols, we can effectively manage suspected cases and minimize the spread of infectious diseases within our communities.。

儿童麻疹合并重症肺炎死亡危险因素分析

河北医药202)年、月第43卷第2期Hebei MedWO JoumO』—)，Vol43Co No.2257 doi：10・3969/j・issn・1002-7396.2021.02.025•论著•儿童麻疹合并重症肺炎死亡危险因素分析孙玲崔晓薇孙一硕周晓强温婵【摘要】目的探讨麻疹合并重症肺炎患儿死亡危险因素，为麻疹合并重症肺炎死亡防控提供依据。

方法回顾性分析201）年至200年确诊并住院治疗的—）名麻疹合并重症肺炎患儿的基本情况、临床特征、实验室检查、治疗和疾病转归等资料，根据疾病转归分为死亡组（14例）和存活组（13）例）；采用单因素分析，比较患儿基本情况、临床症状、实验室检查、呼吸机治疗情况等方面的差异；采用LoyisCo回归分析模型分析患儿死亡的危险因素。

结果—）例麻疹合并重症肺炎患儿中，死亡—例，病死率为-.73%；单因素分析显示：死亡组和存活组在既往病史、现居住地、心肌损害、心力衰竭、呼吸衰竭、CPAP使用天数、有创呼吸机使用天数等方面差异有统计学意义（P<0.0-）；多因素LoyisCo回归分析显示：既往病史（OR二0048,9-%CI：0004-0606）、呼吸衰竭（0R二0067,9-%CI：O006-0793）、有创呼吸机使用天数（0R二0668,95%CI：O497-）.899）是麻疹合并重症肺炎患儿死亡的独立危险因素。

结论患儿既往病史、呼吸衰竭、有创呼吸机使用天数是麻疹合并重症肺炎患儿死亡的独立危险因素。

【关键词】儿童;麻疹;重症肺炎;死亡;危险因素【中图分类号】R-1O）,R563.1【文献标识码】A【文章编号】—02-7386（202））02-0267-04Analysit of risk factort of deyth frem meyslet campycahn by severe pneumoniv in children Analysit of morhlUy riskfactort of meyslet campgcahn w ith severe pnenmonig in chilUren SUN Ling,CUA Xiaopej SUN Yishuo,l t al.HebeiProiccial Children，s Hospital.Hebet,Shathiiang05403)；China【Abshect】Objective To invesCgato the risk factors of death in children with measles comphcaud by severe pneqmoxia,and to provibe evidence for the preven/ox and control of death from measles comphcaud with severe pneqmoxia.Methodt The c/nicai data about O)children pa/ents with measles comphcaud by severe pneqmoxia who were diagnosedand treated in our hospiml from201)to2010were pWospec/veW anaWzed,which included basic igorma/ox,c/nicaifeatures,Wboratom examina/oxs,Weatuent and disease outcome.According to the disease outcome,these pa/ents weredivided into death case group(n=—)and survival case gpup(n=O)).Sinylc factor analysis was used to compare thediRepnces in children；s basic igorma/ox,c/nicai symptoms,Wboratom examina/oxs:and ven/Wtor Weatuent；and UyisCc regression analysis mobei was used t o a—Wze the risk factors of Ueath in the pa/ents.ResnUt Among the O)children withmeasles comphcaud by severe pneqmoxia,—cases died ,with the death rate being5.23%.Univariate analysis showed tha-thew were significant diRepnces in the past medical histom,current residence,myocardial damage,heart failure,pspimtomfailure,and days of CPAP use and the Unyth of invasive ven/Wtor use between death case gpup and survival case group(P<0.2).Mul/va/ato UyisCc regression analysis showed that past medical hisUrp,pspimtom failure and the Unyth of invasiveven/Wtor use were indeqenden-risk OacUrs for death in children with measles comphcaud by severe pneqmoxia.ConclusionThe past medical histom-pspimtom failure,and the Unyth of invasive ven/Wur use arc the indeqenden-risk factors for deathin children pa/ents with measles comphcaud by severe pneqmoxia.【Key wo U s t children；measles;severe pneqmoxia；death；risk factors麻疹是由麻疹病毒引起的一种具有高度传染性的急性出疹性传染病,麻疹感染的主要人群为儿童九29。

门诊药学实验总结英语作文

门诊药学实验总结英语作文Title: Summary of Outpatient Pharmacy Experiment。

Introduction:The outpatient pharmacy experiment was conducted as part of the pharmacy curriculum to provide students with practical experience in dispensing medications and interacting with patients. This essay aims to summarize the key aspects of the experiment, including its objectives, methods, results, and personal reflections.Objectives:The primary objective of the outpatient pharmacy experiment was to enhance students' understanding andskills in medication dispensing. By actively participating in the experiment, students were expected to gain practical knowledge in various aspects, such as medication labeling, patient counseling, and prescription interpretation.Additionally, the experiment aimed to improve students' communication skills and professionalism when dealing with patients.Methods:The experiment was conducted in a simulated outpatient pharmacy setting, where students were assigned different roles, including pharmacists, pharmacy technicians, and patients. Each student had the opportunity to rotate through these roles during the experiment to gain a comprehensive understanding of the entire process. The experiment was divided into several stages, starting from prescription interpretation, medication preparation,patient counseling, and medication dispensing. Students were provided with mock prescriptions, which they had to accurately interpret and dispense according to thepatient's needs and medication safety guidelines. The experiment also involved patient counseling sessions, where students had to effectively communicate important information regarding medication usage, potential side effects, and drug interactions.Results:The outpatient pharmacy experiment yielded several positive outcomes. Firstly, students demonstrated an improved understanding of prescription interpretation, ensuring accurate dispensing of medications. They also developed efficient medication preparation skills, adhering to proper dosage calculations and compounding techniques. Moreover, students displayed enhanced communication skills during patient counseling sessions, effectively conveying crucial information to ensure safe and appropriate medication use. The experiment also helped students develop a sense of professionalism and empathy towards patients, understanding the importance of patient-centered care.Personal Reflections:Personally, this experiment was a valuable learning experience. It provided me with hands-on exposure to various aspects of pharmacy practice, allowing me to apply theoretical knowledge in a practical setting. Theexperiment enhanced my ability to interpret prescriptions accurately and dispense medications safely. It also improved my communication skills, as I learned how to effectively counsel patients on medication usage and address their concerns. Additionally, the experiment highlighted the importance of attention to detail and professionalism in the pharmacy profession, which will undoubtedly shape my future practice.Conclusion:The outpatient pharmacy experiment served as an effective means to enhance students' understanding and skills in medication dispensing and patient counseling. Through active participation and rotation of roles, students gained practical knowledge and improved their communication skills. This experiment not only provided valuable insights into the pharmacy profession but also instilled a sense of professionalism and empathy towards patients. Overall, the outpatient pharmacy experiment was a significant milestone in my pharmacy education, equipping me with essential skills for future practice.。

学术英语（医学）单词填空及答案

学术英语（医学）单词填空及答案学术英语（医学）课后词组Unit11．overload神经过载2.a typical典型的诊所就诊3.DEXA DEXA扫描4.medical ⾏医5. control⾎压控制6.health健康保持7. report乳房X线检查报告8. examination体检9. of a medication药物的副作⽤10.perpetual永久的恐慌11. physicians职业医⽣12. field移植领域13.medical医疗预算14.paracetamol 扑热息痛药⽚15. cap防孩⼦打开的盖⼦16. clinical trial随机临床试验17.Random随机分配18.patient病⼈的预后19. group对照组20.a10-year study10年的跟踪研究21.a medical内科病房22.infectious 传染性肝炎23.Severe⾝体严重不适24.bilirubin胆红素代谢25.permanent damage永久的肝损伤26.exacerbate 加重病理⽣理状况27.Medical医学⽂献28.clinical 临床调查29. of relapse复发率30.clinical 临床流⾏病学31.strict 严格的卧床休息32.hospital住院33.recurrent 反复发作的黄疸34.clinical临床病程35 morphine静脉注射吗啡36 blood pressure舒张压37.brain ⼤脑⾎灌输38. care初级保健39.aorto-coronary arterial 主动脉冠状动脉旁路40. treatment decision知情治疗决41.an international group ⼀个国际⼈道组织42.the Red红⼗字会43.The first major effort第⼀次重⼤援助⼯作44 of war战争中的⼈员伤亡45. relief efforts紧急援助、Unit21 disease(再现疾病)2.new flu新流感变种3.antibiotics and抗⽣素和疫苗4. disease传染病5 disease新现疾病6 strategy预防策略7.bubonic腺⿏疫8. microbes病原微⽣物9.public heath 公共卫⽣机构10.drug 抗药性11.an of antibiotic therapy 抗⽣素治疗疗程12.scarlet 猩红热13.the level of 毒性⽔平14.flu流感⼤流⾏15.surface表⾯抗原16. shift基因改变17.neurological 神经性并发症18.waning of 免疫⼒减弱19.public health公共卫⽣基础设施20.a malaria⼀个疟疾病例21. flu猪流感22. bacillus结核杆菌23.the of morbidity发病率⽔平24.health保健专业⼈⼠25 tuberculosis潜伏结核病26.tuberculin 结核素⽪试27. programmes 筛查计划 28. gamma tests γ⼲扰素测试 29.drug 药物毒性 30.an disease ⼀种可治愈的病 31, infectious disease 难治的传染病 32.an unknown ⼀种未知的病原体33.chronic gastric 慢性胃溃疡 34 to carries of disease 接触带病者 35,genetic 基因重组 36.agent of ⽣物恐怖活动病原 37. infections 通过⾷物传播的传染病 Unit 31.the surge of 肾上腺素激增2.an internal medicine 内科实习期3.an disease ⾃体免疫4.loss of 丧失持久⼒5. weakness 短暂的虚弱6.becoming 卧床不起7.a building 基本构件8.an animal 动物模型9.to slow 减缓神经退化 10.to toxins 排除毒素 11.to nutrition 优化营养 12.toxic 毒素载量13.the risk of 复发危险 14.physician 医⽣⾃我实验 15.a clinical 临床试验16. electrical stimulation 神经肌⾁电刺激17.physical 理疗师18.the impact of 微量营养素的影响 19.brain 脑功能2 the emotional flow 跟踪情绪波动 21 of emotions 情绪协调 22. reactions ⼼⾎管反应25.emotional 情绪传染互相调节27.a ⽣物⼼理单元 28.emotional 情感慰藉29.functional resonance 功能性磁共振成像 30.to brain zones 激活该脑部区域 31.to make it 使之成为强制性 32.a project ⽆把握的项⽬ 33.medical background 医学背景 4.proof of 概念验证35.dose 剂量⽅案36. or concomitant conditions 并发症与合并症37 agents 抗肿瘤的药剂 38.standard 标准疗法39. properties 药理学特性 40.poor 溶解性差41. pharmacology 体内药理学 Unit 41. medicine 补充医学2. medicine 替代医学3.a medical 医疗模式4. and herbs 针灸和草药5.a treatment 辅助治疗6. a and vomiting 恶⼼，呕吐7. dental pain 术后⽛痛 . trials 临床试验9. therapy 物理疗法，理疗 10 modalities 治疗⽅法 11.a therapeutic 治疗⼲预 12.Research design 研究设计 13.magnetic e 磁共振14.positron tomography 正电⼦发射型计算机断层成像15 effect ⽌痛效果16.biomedical ⽣物医学界 17. unit 康复中⼼18. acupuncturist 持照针灸师 19.therapeutic 治疗策略 20.herbal 草药配⽅21.a wide array of 各式各样的并发症 22. East-West medicine 中西医结合23. abdominal pain 急性腹痛 24.to medicines 施药，⽤药 25.surgical 外科⼿术 26.scientific 科学评估 27. statistics 患病率统计 prevalence28. therapies传统疗法29. models of care询证医学模式30.stress压⼒处理31 nervous system周围神经系统.peripheral32.physiologic⽣理机制33.mechanistic and studie s机制和还原式研究34. research效益研究35.clinical临床结果36. and clinical studies临床前及临床研究37 mechanisms可能的机制38 therapies推拿治疗39. medicine顺势疗法40. medicine⾃然疗法41. and yoga冥想与瑜伽Unit51.a health健康危机2.physical s⾝体症状3.Energy and能量和活⼒4.be completely I from sth.对某事完全免疫5. of falseness虚假的病毒6.stressful有压⼒的⽣活⽅式7. t emotion健全的感情8. health脆弱的健康9.to our mind,body and spirit平衡⼼理、⾝体和精神10. life精神⽣活11.the to wellness通向⾝⼼健康的“路障”12. emotions被压抑的感情13. feelings and emotion真情实感14. l influences⼼理影响15.fully human beings⼗全⼗美的⼈16. teeth蛀⽛17 professor营养教授18.burgeoning迅速膨胀的腰围19. water瓶装⽔20.caloric热量摄⼊21.to curb节制⾷欲22.grains and⾕物和蛋⽩质23.childhood ⼉童肥胖症24 protein精益蛋⽩质25. habits饮⾷习惯26. of life⽣活质量27. category乳制品类28.prevention of 糖尿病的预防29.sodium钠的含量Unit61. homes养⽼院2 care临终关怀3.congestive heart充⾎性⼼衰4.available 24⼩时随叫随到5 care unit冠⼼病监护室6.to to treatment对治疗有反应7.skilled nursing专业护理机构8. care⽣命终末期护理9. care舒适护理10.hospital planner出院计划专员11 care症状护理12 care姑息疗法13. illness绝症14.chronic obstructive disease慢性阻塞性肺病15. treatments实验性治疗16.spiritual精神顾问17.to all treatment终⽌所有治疗18.to go through经历透析19.A PAP 巴⽒涂⽚检查20.patient- relationship医患关系21.to provide 提供常规医护22. examinations预防性检查23.off the path离开熟路，另辟蹊径24.to into a shape塑形25.To a prescription照旧处⽅再开药26.in vitro体外受精27. biology基础⽣物学28.embryonic research胚胎⼲细胞研究29.to with an outside与圈外⼈合作30.a baby试管婴⼉31. sciences⽣殖科学32.to administer施⽤激素33.to isolate eggs分离未成熟卵⼦34. observations经验观察35. work⾸创研究36.a fibre-optic光导纤维内窥镜37. guidelines伦理原则38.societal社会关注39. couples不孕不育夫妇40. disease遗传疾病41.Cystic 囊泡性纤维症42.ethical伦理困境Unit71.a nursing护⼠站2. machines⽣命维持系统/doc/a0db7416aff8941ea76e58fafab069dc5122479d.html fort 舒适护理措施4.to treatments停⽌治疗5. decision-making process家长式决策程序6.patient给病⼈授权7.medical医学伦理学家8.ethical 伦理准则9.clinical临床理念10. care以病⼈为中⼼的护理11.patient病⼈⾃主权12.treatment治疗选择13. purview专属领域14. decisions紧急状况下做的决定15.physician对医⽣的限制16. and confusion焦虑与困惑17.ethical违背伦理18.family家庭医疗19.widespread⼴泛转移20. treatment积极治疗21 lesion原发病灶22.to recommend 建议随访23.electronic电⼦病历24.pulmonary肺栓塞/doc/a0db7416aff8941ea76e58fafab069dc5122479d.html puterized计算机断层扫描CT26.bilateral 双侧浸润27.a X-ray X线胸⽚28.left pneumonia左下肺叶肺炎29. breathing呼吸困难30.the hospice临终关怀团队31. illness慢性病32 aspects社会⼼理学领域33.evidence-based循证临床指南34.to a plan of care实施治疗⽅案Unit81.human⼈体研究对象2. research⽣物医学研究3.accepted公认的治疗4.a formal正式⽅案5.the principle of有利原则6.the principle of公正原则7. agents有⾃主能⼒的⾏为者8. autonomy⾃主性减弱9.be risk of harm使……⾯临受害危险10.Hippocratic希波克拉底誓⾔11.fairness in分配的公正性/doc/a0db7416aff8941ea76e58fafab069dc5122479d.html rmed知情同意13.fair and outcomes公正的程序和结果14.the table⼿术台15.an ethical伦理责任16.a neurosurgeon⼉科神经外科医⽣pediatric17.to the surgery做⼿术18.blood ⾎流19. care重症监护20. father义⽗21. father⽣⽗22. needs⼼理需要23. judgment医学判断24. therapy职业疗法25.to meningitis感染脑膜炎26.to die of an 死于感染27.blood⾎管28.imbalances in循环的不平衡29.the of human research subjects ⼈类研究对象的安宁30.to approve or all research activi ties批准或不批准所有的研究活动31.to review a审查⼀个研究计划32.at risk of civil or criminal有民事或刑事责任的危险参考答案Unit 11. neuron 神经2. office visit(诊所)就诊3. scan 扫描4. medical practice ⾏医5. blood pressure ⾎压6. maintenance(健康)保持7. mammogram 乳房Ｘ线8. physical ⾝体9. side effect 副作⽤10. panic 恐慌11. practicing 执业12. transplant 移植13. budget 预算14. tablet 药⽚15. childproof 防孩⼦16. randomized 随机17. allocation(随机)分配18. prognosis 预后19. control 对照20. follow-up 跟踪21. ward 病房22. hepatitis 肝炎23. malaise ⾝体不适24. metabolism 代谢25.liver 肝26.pathophysiology 病理⽣理27. literature ⽂献28. investigation 调查29. incidence 率30. epidemiology 流⾏病学31. bed rest 卧床休息32. hospital stay 住院33. jaundice 黄疸34. course 病程35. intravenous 静脉注射36. diastolic 舒张37. perfusion 灌注38. primary 初级39. bypass(冠脉)旁路40. informed 知情41. humanitarian ⼈道主义42. the Red Cross 红⼗字会43. relief 援助44. casualty ⼈员伤亡45. emergency 紧急Unit 21. re-emerging 再现2. strain 变种3. vaccine 疫苗4. infectious 传染性的5. emerging 新出现6. prevention 预防7. plague ⿏疫8. pathogenic 病原的9. authorities 机构10. drug resistanc 抗药性11. course 疗程12. scarlet fever 猩红热13. virulence 毒性14. pandemic ⼤流⾏15. antigen 抗原16. genetic 基因的17. neurological 神经性18. immunity 免疫⼒19. infrastructure 基础设施20. case 病例21. swine 猪22. tuberculosis 结核23. morbidity/incidence 发病率24. professionals 专业⼈⼠25. latent 潜伏26. skin test ⽪试27. screening 筛查28. interferon ⼲扰素29. toxicity 毒性30. curable 可治愈的31. intractable 难治的32. pathogen 病原体33. ulcer 溃疡34. exposure 接触(带病者)35. recombination 重组36. bioterrorism ⽣物恐怖活动37. foodborne ⽣物传播Unit 31. adrenaline 肾上腺素2. residency 实习3. autoimmune ⾃⾝免疫4. stamina 持久⼒5. transient 短暂的6. bedridden 卧床不起7. building block 基本构件8. model 模型9. neurodegeneration 神经退化10.excrete 排除(毒素)11.optimize 优化12.load 载量13.relapse 复发14.self-experimentation ⾃我实验15.trial 试验16.neuromuscular 神经肌⾁17.therapist 治疗师18.micronutrient微量营养素19.function 功能20.track 跟踪21.coordination 协调22.cardiovascular ⼼⾎管23.rapport 亲密24.synchronization 同步25.contagion 传染26.regulate 调节27.psychobiological⽣物⼼理28.solace 慰藉29.imaging ＭＲＩ30.activate 激活31.mandatory 强制性32.dubious ⽆把握的33.background 背景34.concept 概念35.regimen ⽅案/doc/a0db7416aff8941ea76e58fafab069dc5122479d.html plications 并发症37.anti-tumor 抗肿瘤38.standard 标准的39.pharmacological 药理学的40.solubility 溶解性41.in vivo 体内Unit 41. complementary 补充2. alternative 替代(医学)3. paradigm 模式4. acupuncture 针灸5. adjunct 辅助6. nausea 恶⼼7. post-operative 术后8. clinical 临床的9. physical therapy 理疗10. therapeutic 治疗(⽅法)11. intervention ⼲预12. design 设计13. resonance 共振14. emission 发射ＰＥＴ15. analgesia ⽌痛16. establishment(⽣物医学)界17. rehabilitation 康复18. licensed 持照(针灸师)19. strategies 策略20. formulas 配⽅21. wide array 各式各样的22. integrative(中西医)结合23. acute 急性的24. administer 给药25. procedure 程序26. evaluation 评估27. prevalence 患病率28. conventional 传统(疗法)29. evidence-based 循证的30. management(压⼒)处理31. peripheral 外周／外围32. mechanisms 机制33. reductionistic 还原式的34.cost-effectiveness 效益35. outcomes 结果36. preclinical 临床前37. plausible 可能的38. manipulative 推拿39. homeopathic 顺势40. naturopathic ⾃然(疗法) 41. meditation 冥想Unit 51. crisis 危机2. symptoms 症状3. vitality 活⼒4. immune 免疫5. virus 病毒6. lifestyle ⽣活⽅式7. robust 健全的8. fragile 脆弱的9. balance 平衡10. spiritual 精神的11. blockages 路障12. repressed 被压抑的13. genuine 真实的(真情实感)14. physiological ⼼理15. integrated 整合的(⼗全⼗美)16. decaying teeth 蛀⽛17. nutrition 营养18. waistline 腰围19. bottled 瓶装(⽔)20. intake 摄⼊21. appetite ⾷欲22. protein 蛋⽩质23. obesity 肥胖症24. lean 精益的(蛋⽩质)25. dietary 饮⾷(习惯)26. quality 质量27. dairy 乳制品28. diabetes 糖尿病29. content 含量Unit 61. nursing home 养⽼院2. hospice 临终(关怀)3. failure(⼼)衰4.availablearound-the-clock24⼩时随叫随到5. coronary 冠⼼病6. respond(对治疗有)反应7. facility 机构8. end-of-life 终末期9. comfort 舒适的(护理)10. hospital discharge 出院11. care(症状)护理12. palliative 姑息的13. fatal illness 绝症14. pulmonary 肺的ＣＯＰＤ15. experimental 实验性的16. advisors 顾问17. discontinue 终⽌18. dialysis 透析19. smear 涂⽚20. provider 医患关系21. care-as-usual 常规医护22. preventive 预防性23. beaten 常⽤的off the beaten path 离开熟路,另辟蹊径24. mold into the shape 塑形25. renew 重新开始to renew a prescription 照旧处⽅再开药26. fertilization 授精27. basic 基础的(⽣物学)28. stem cell ⼲细胞29. collaborate 合作30. test-tube 试管(婴⼉)31. reproductive ⽣殖的32. hormones 激素33. immature 未成熟的34. empirical 经验(观察) 35.pioneering ⾸创的36. endoscope 内镜37. ethical 伦理的38. concern(社会)关注39. infertile 不孕不育的40. inherited 遗传性的41. fibrosis 纤维化42. dilemmas 困境Unit 71. station(护⼠)站2. life-support ⽣命维持(系统)3. measures 护理措施4. withdraw 停⽌(治疗)5. paternalistic 家长式的6. empowerment 授权7. ethicists 伦理学家8. principles 准则9. ideal 理念10.patient-centered 以病⼈为中⼼的11. autonomy ⾃主权12. options 选择13. exclusive purview 专属的(领域)14. emergency 紧急(决定)15. restraint 限制16. anxiety 焦虑17. transgression 违背18. practice(家庭)医疗19. metastases(⼴泛)转移20. aggressive 积极的21. primary 原发22. follow-up 随访23. record 病历24. embolism 栓塞25. tomography 断层摄像ＣＴ26. infiltrates 浸润27. chest 胸28. lower-lobe 左下叶29. labored(呼吸)困难30. team 团队31. chronic 慢性的32. psychosocial 社会⼼理33. guidelines 指南34. implement 实施(治疗⽅案)Unit 1 动脉旁路1.neuron overload 神经过载2.a typical office visit 典型的诊所就诊3.DEXA scan DEXA扫描4.medical practicing ⾏医5.blood pressure control⾎压控制6.health maintenance 健康保持7.Mammogram report 乳房X线检查报告8.physical examination 体检9.side effect of amedication 药物的副作⽤10.perpetual panic 永久的恐慌11.practicing physicians 职业医⽣12.transplant field 移植领域13.medical budget 医疗预算14.paracetamol tablet 扑热息痛药⽚15.childproof cap 防孩⼦16.randomized clinical trial 随机临床试验17.Random allocation 随机分配18.patient prognosis 病⼈的预后19.control group 对照组20.a 10-year follow-up study 10年的跟踪研究21.a medical ward 内科病房22.infectious hepatitis 传染性肝炎23.Severe malaise ⾝体严重不适24.bilirubin metabolism 胆红素代谢25.permanent liver damage 永久的肝损伤26.exacerbate pathophysiology 加重病理⽣理状况27.Medical literature 医学⽂献28.clinical investigation 临床调查29.incedence of relapse 复发率30.clinical epidemiology 临床流⾏病学31.strict bed rest 严格的卧床休息32.hospital stay 住院33.recurrent jaundice 反复34.clinical course 临床病程35.intravenous morphine静脉注射吗啡36.diastolic blood pressure舒张压37.brain perfusion ⼤脑⾎灌输38.primary care初级保健39.aorto-coronary arterialbypass主动脉冠状助⼯作/doc/a0db7416aff8941ea76e58fafab069dc5122479d.html rmed treatment decision 知情治疗决41.an internationalhumanitarian group⼀个国际⼈道组织42.the Red Cross 红⼗字会43.The first major reliefeffort 第⼀次重⼤援44.casualty of war 战争中的⼈员伤亡45.emergency relief efforts紧急援助Unit 31.the surge of adrenaline肾上腺素激增2.an internal medicineresidency 内科实习期3.an autoimmune disease ⾃体免疫4.loss of stamina 丧失持久⼒5.transient weakness 短暂的虚弱6.becoming bedridden 卧床不起7.a building block基本构件8.an animal model 动物模型9.to slow neurodegeneration减缓神经退化10.to excrete toxins排除毒素11.to optimize nutrition 优化营养12.toxic load毒素载量13.the risk of relapse 复发危险14.physicianself-experimentation医⽣⾃我实验15.a clinical trial 临床试验16.neuromuscular electrical stimulation 神经肌⾁电刺激17.physical therapist 理疗师18.the impact of micronutrients 微量营养素的影响19.brain function 脑功能20.track the emotional flow 跟踪情绪波动21.coordination of emotions 情绪协调22.cardiovascular reactions ⼼⾎管反应23.feeling of rapport 亲密感觉24.rapid entrain 迅速同步25.emotional contagion 情绪传染26.to mutually regulation互相调节27.a psychobiological unit⽣物⼼理单元28.emotional solace情感慰藉29.functional magneticresonance imaging功能性磁共振成像30.to activate brain zones激活该脑部区域31.to make it mandatory使之成为强制性32.a(n) dubious project⽆把握的项⽬33.medical background医学背景34.proof of concept概念验证35.dose regimen 剂量⽅案/doc/a0db7416aff8941ea76e58fafab069dc5122479d.html plications or concomitant conditions并发症与合并症37.anti-tumor agents 抗肿瘤的药剂38.standard therapy标准疗法39.pharmacologyproperties 药理学特性40.poor solubility 溶解性差41.in vivo pharmacology体内药理学Unit 51.a health crisis 健康危机2.physical symptoms ⾝体症状3.Energy and vitality 能量和活⼒4.be completely immunefrom sth.对某事完全免疫5.virus of falseness 虚假的病毒6.stressful lifestyle 有压⼒的⽣活⽅式7.robust emotion 健全的感情8.fragile health 脆弱的健康9.to balance ourmind ,body and spirit平衡⼼理、⾝体和精神10.spiritual life精神⽣活11.the blockage to wellness通向⾝⼼健康的“路障”12.repressed emotions 被压抑的感情13.genuine feelings and emotion真情实感14.physiological influences ⼼理影响15.fully integrated human beings ⼗全⼗美的⼈16.decaying teeth 蛀⽛17.nutrition professor 营养教授18.burgeoning waistline 迅速膨胀的腰围19.bottled water 瓶装⽔20.caloric intake 热量摄⼊21.to curb appetite 节制⾷欲22.grains and protein ⾕物和蛋⽩质23.childhood obesity ⼉童肥胖症24.lean protein 精益蛋⽩质25.dietary habits 饮⾷习惯26.quality of life ⽣活质量27.diary category 乳制品类28.prevention of diabetes 糖尿病的预防29.sodium content 钠的含量Unit 71.a nursing station 护⼠站。

医学英语写作详解

医学英文摘要写作How to write a medical English abstract第一章概述一、摘要的定义、用途、和长度二、摘要的内容三、摘要的类型四、摘要的写作格式五、摘要写作的注意事项What is an abstract?An abstract is a brief summary of the most important points in a scientific paper.摘要是作者研究过程、研究目的、研究方法和研究结果的简要陈述和概括。

Purposes for AbstractsAbstracts typically serve five main goals:Help readers decide if they should read an entire articleHelp readers and researchers remember key findings on a topicHelp readers understand a text by acting as a pre-reading outline of key points Index articles for quick recovery and cross-referencingAllow supervisors to review technical work without becoming bogged down in details二、摘要的内容Contents1. Title2. Name of the author3. Unit of the author/address4. Text of the abstract5. Keywords1）目的2）方法3）结果4）结果的分析、比较、评价以及应用，提出的问题以及建议5）其他三、摘要的类型1. descriptive abstract ——描述性摘要2. informative abstract——资料性摘要3. descriptive-informative abstract——描述-资料性摘要1. Non-structured abstract （非结构式摘要）2. Structured abstract （结构式摘要）full-structuredsemi-structured1.描述性摘要Descriptive Abstract/ Indicative AbstractThe descriptive abstracts tell what topics are taken up in the paper. They contain indicative information on purpose, scope, or methodology in the original documents, but mention little or nothing about details of results, conclusions or recommendations. The advantages of a descriptive abstract are that it is easy to write and is usually short; a serious disadvantage is that it contains little information.一般只用两三句话概括论文或报道的主题，而不涉及具体的数据和结论，通常用于综述、会议报告等。

2021医学考研复试：呼吸内科[SC长难句翻译文]

SCI长难句呼吸内科第一章—社区获得性肺炎Community-acquired pneumonia is still a significant cause of morbidity and mortality and is often misdiagnosed and inappropriately treated.Although it can be caused by a wide variety of micro-organisms, the pneumococcus,atypicals,Staphylococcus aureus and certain Gram-negative rods are the usual pathogens encountered.Antimicrobial therapy should be started as soon as possible particularly in those requiring admission to hospita.社区获得性肺炎仍然具有很高的发病率和死亡率，且经常被误诊和不恰当地治疗。

虽然它可以由多种微生物引起，但涉及的常见病原体有肺炎球菌、非典型球菌、金黄色葡萄球菌和某些革兰氏阴性杆菌。

特别是（对于）那些需要住院的患者，抗菌治疗应尽快开始。

知识点总结：1pneum(o)-前缀，肺2pneumonia n.肺炎3pneumococcus n.肺炎球菌4atypical adj.非典型的5Staphylococcus aureus n.金黄色葡萄球菌6Gram-negative rods n.革兰氏阴性杆菌7pathogen n.病原体8antimicrobial adj.抗菌的Mandell munity-acquired pneumonia:An overview.Postgrad Med.2015 Aug;127(6):607-15.SCI长难句呼吸内科第二章—肺脓肿A lung abscess is an infectious pulmonary disease characterised by the presence of a pus-filled cavity within the lung parenchyma.The content of an abscess often drains into the airways spontaneously,leading to an air-fluid level visible on chest X-rays and CT scans. Primary lung abscesses occur in patients who are prone to aspiration or in otherwise healthy individuals;secondary lung abscesses typically develop in association with a stenosing lung neoplasm or a systemic disease that compromises immune defences,such as AIDS,or after organ transplantation.肺脓肿是一种感染性肺部疾病，其特征是肺实质内有充满脓的空洞。

1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。

Clinical InvestigationOutcomes in Patients Treated With Mastectomy for Ductal Carcinoma In SituDawn Owen,MD,PhD,FRCPC,*Scott Tyldesley,MD,MPA,FRCPC,*,yCheryl Alexander,CHIM,y Caroline Speers,BA,y Pauline Truong,MD,FRCPC,*,yAlan Nichol,MD,FRCPC,*,y and Elaine S.Wai,MD,MS,FRCPC*,y*Radiation Therapy Program and y Breast Cancer Outcomes Unit of the British Columbia Cancer Agency and University of British Columbia,Vancouver and Victoria,British Columbia,CanadaReceived Jul8,2012,and in revised form Oct4,2012.Accepted for publication Oct13,2012SummaryThere are few studies inves-tigating whether subgroups of women treated with mastectomy for DCIS have a higher than expected risk of LRR so that PMRT could be justiﬁed.This study attempted to identify such a subgroup in a population-based cohort.With a median follow-up of12.0years,the 10-year LRR was1.0%.No subgroup had LRR>10%, supporting the omission of PMRT as routine care for DCIS treated with mastectomy.Purpose:To examine,in a large,population-based cohort of women,the risk factors for recur-rence after mastectomy for pure ductal carcinoma in situ(DCIS)and to identify which patients may beneﬁt from postmastectomy radiation therapy.Methods and Materials:Data were analyzed for637subjects with pure DCIS,diagnosed between January1990and December1999,treated initially with mastectomy.Locoregional relapse(LRR),breast cancer-speciﬁc survival,and overall survival were described using the Kaplan-Meier method.Reported risk factors for LRR(age,margins,size,Van Nuys Prognostic Index,grade,necrosis,and histologic subtype)were analyzed by univariate(log-rank)and multi-variate(Cox modeling)methods.Results:Median follow-up was12.0years.Characteristics of the cohort were median age55 years,8.6%aged 40years,30.5%tumors>4cm,42.5%grade3histology,37.7%multifocal disease,and4.9%positive margins.At10years,LRR was1.0%,breast cancer-speciﬁc survival was98.0%,and overall survival was90.3%.All recurrences(n Z12)involved ipsilateral chest wall disease,with the majority being invasive disease(11of12).None of the12patients with recurrence died of breast cancer;all were successfully salvaged(median follow-up of4.4years). Ten-year LRR was higher with age 40years(7.5%vs1.5%;P Z.003).Conclusion:Mastectomy provides excellent locoregional control for DCIS.Routine use of post-mastectomy radiation therapy is not justiﬁed.Young age( 40years)predicts slightly higher LRR,but possibly owing to the small number of cases with multiple risk factors for relapse, a subgroup with a high risk of LRR(ie,approximately15%)was not identiﬁed.Ó2012Elsevier Inc.Reprint requests to:Scott Tyldesley,MD,MPA,FRCPC,British Columbia Cancer Agency,Vancouver Centre,600West10th Avenue, Vancouver,British Columbia,Canada V5Z4E6.Tel:604-877-6000;Fax: (604)877-0505;E-mail:styldesl@bccancer.bc.caPresented in part at the Canadian Association of Radiation Oncologists 2010Annual Conference,(September22-24,2010)Vancouver,BC, Canada.This work was funded in part by operating grants(E.S.W.)from the Canadian Breast Cancer Foundation,BC/Yukon Chapter,and the Canadian Breast Cancer Research Alliance,DEX grant(#015701).S.T.is a recipient of a Career Investigator Award from the Michael Smith Foundation for Health Research.Conﬂict of interest:none.Int J Radiation Oncol Biol Phys,V ol.-,No.-,pp.1e6,20120360-3016/$-see front matterÓ2012Elsevier Inc.All rights reserved. /10.1016/j.ijrobp.2012.10.020Radiation Oncology International Journal of biology physicsIntroductionApproximately15%-20%of new breast cancer diagnoses are pure ductal carcinoma in situ(DCIS)(1).The incidence of DCIS has increased signiﬁcantly over the last20years with the advent of widespread screening mammography(2).Most women who are diagnosed with DCIS are treated with breast-conservation surgery (BCS)with or without adjuvant radiation therapy(RT).Although there are no prospective randomized trials directly comparing the outcomes of mastectomy versus BCS plus RT for DCIS,several retrospective studies have reported that these treatments provide similar locoregional control and overall survival(3-6).In extrapolating from National Surgical Adjuvant Breast and Bowel Project protocol B-06,78women were found to have DCIS,and in those treated with mastectomy the locoregional recurrence rate was only2%(7).Mastectomy is the treatment of choice in women with multi-centric or diffuse DCIS or women who are not candidates for RT (8-10).The recurrence rate after mastectomy is reported to be1%-3%(3,6,11),although some studies suggest that the recurrence rate after mastectomy may be5%-7%(12,13)and as high as16%in some subjects with high-risk characteristics(14).The majority of locoregional recurrences are invasive breast cancers(3,6,12,14).The present study examined the risk factors for recurrence after mastectomy for pure DCIS,to identify which patients may beneﬁt from postmastectomy radiation therapy(PMRT).Methods and MaterialsAn analysis of women diagnosed with pure DCIS between January1990and December1999in British Columbia and treated initially with mastectomy was performed.Data were abstracted from the prospectively collected Breast Cancer Outcomes Unit and retrospectively collected DCIS Outcomes Database(15).This period coincided with the implementation of a population-based screening mammography program in British Columbia(16). This study was approved by the British Columbia Cancer Agency Research Ethics Board.Patients with synchronous invasive breast cancer,previous invasive cancer of any site,contralateral DCIS,DCIS with microinvasion,male gender,mixed or second histologies such as Paget’s disease or lobular carcinoma in situ,and patients treated with breast-conserving therapy were excluded.All patients who experienced disease relapse were identiﬁed,and individual infor-mation from electronic and paper charts was reviewed.Data were collected on age at diagnosis,tumor size,tumor grade,margin status,histology,presence of comedocarcinoma, necrosis,and multifocality.Axillary node dissection was per-formed in392women,213did not have any nodal surgery,none had sentinel node biopsies,and for53women it was unknown whether axillary surgery was performed.None had positive nodes. Only9patients received RT in this cohort;these patients were excluded from analysis.Pathologic data were gleaned from paper and electronic pathology reports;a formal pathology review of slides was not performed.Estrogen receptor status was missing for most patients because it was not routinely performed for DCIS during the study era.In British Columbia the use of tamoxifen was not approved or funded for patients with DCIS until2000,so few if any patients in the1990s would have been offered tamoxifen. Surgical margins were categorized as negative( 2mm),close (<2mm),or positive(tumor touching ink),according to theBreast Cancer Outcomes Unit data abstraction guidelines.Data onthe use of breast reconstruction and skin-sparing mastectomy werenot available.Oncologic outcomes including locoregional relapse(LRR),breast cancer-speciﬁc survival(BCSS),and overall survival(OS)were described using the Kaplan-Meier method and comparedusing the log-rank test.Risk factors(age at diagnosis,histologicsubtype,nuclear grade,size,comedocarcinoma,necrosis,andmargin status)for subjects with and without LRR were comparedusing univariable tests:c2for categoric variables and t test for parametric variables.Log-rank test was used to compare LRR forindividual variables.These variables were also entered into a Coxregression analysis.Tumor size was categorized because of difﬁ-culties assessing exact size on multiple pathology reports.Coxmodeling was used to assess the effect of risk factors on OS andBCSS.The impact of Van Nuys Prognostic Index(VNPI)(17)onrisk of LRR was assessed with Cox regression analysis.The VNPIcombines age,nuclear grade plus necrosis,margin status,andtumor size to predict LRR in DCIS patients treated with BCS(17).For variables that included an unknown category(eg,marginstatus)when the analysis was run,the unknowns were excluded.Statistical signiﬁcance was deﬁned as P<.05.All statistical anal-yses were performed using the Statistical Package for SocialSciences,version14.0(SPSS,Chicago,IL).ResultsPatient characteristicsDuring the study era,2805patients were diagnosed with pureDCIS.Of these,646patients were treated with mastectomy,forming the study cohort.Nine patients received postmastectomyradiation and were excluded from our analysis.Median follow-upwas12.0years(range,0.14-18.4years).Table1summarizes thesubjects’demographic and pathologic characteristics.Median ageat diagnosis was55years(range,27-92years).A total of42.5%ofpatients had grade3disease(n Z271),and57%had come-docarcinoma(n Z362).Positive margins were identiﬁed in4.9%of patients(n Z31).Multifocal disease was present in37.7%ofmastectomy specimens(n Z240)and30.5%(n Z194)had tumorsize>4cm.OutcomesTen-year OS was90.3%,and15-year OS was83.4%.Ten-yearBCSS was98.0%,and15-year BCSS was98.0%.The10-year LRRwas1.0%,and15-year LRR was2.1%.No histologic or patientcharacteristics impacted OS or BCSS.Of the11patients whoeventually died of breast cancer,none had a record of a localrelapse,2had axillary relapses as site ofﬁrst relapse,then subse-quent metastases,and2had contralateral breast cancer that went onto metastasize.The remaining7patients developed distant metas-tasis,with or without axillary relapse,as theirﬁrst site of relapse. Factors affecting LRROn univariable analysis,only1factor was signiﬁcantly associatedwith an increased10-year risk of LRR:age 40years(7.5%vs1.5%;log-rank test,P Z.003;Fig.1).On Cox regression analysis,Owen et al.International Journal of Radiation Oncology Biology Physics 2age conferred an increased risk of LRR(P Z.014).The VNPI had no impact on LRR.We also looked at the effect of close or positive margins in the subset of women aged 40years.There were55women in the subgroup,with10having close/positive margins.The LRR in these young women with close/positive margins was10%,versus 6.7%in those with negative margins(P Z.683),which was not statistically different.Recurrence characteristicsThe clinicopathologic characteristics of the12patients who experienced LRR are summarized in Table2.All recurrences occurred in the ipsilateral chest wall,and most(11of12)were invasive breast cancer.Four of the12women who recurred were aged<40years.All recurrences were treated with surgical exci-sion and adjuvant RT.None of the women with recurrent disease died from breast cancer,and none have had a subsequent relapse after salvage treatment(Table2).DiscussionDuring the study period,approximately25%of all patients(646of 2805)presenting with pure DCIS were treated with mastectomy in British Columbia.Over this period,the evidence for breast-conserving therapy improved,and the policy regarding the role of mastectomy evolved to have a more limited indication in British Columbia.The British Columbia Cancer Agency treatment policy by the end of the study era stated that mastectomy was indicated for those with“very diffuse areas of DCIS(eg,>5cm or 1/4of the breast).”The10-year LRR of1.0%in our study cohort is comparable to other institutional series and meta-analyses(6,17). In the present series,all recurrences were in the ipsilateral chest wall,and most were invasive breast cancer,consistent with prior studies reporting that80%-90%of postmastectomy recurrences were invasive chest wall disease(6,8,18).In this study,3of the recurrences also had ipsilateral axillary involvement.However,all patients were successfully salvaged,and none died of breast cancer.Subjects aged 40years had a4-fold increased risk of LRR compared with subjects aged>40years.Prior studies of DCIS suggest that young age(variably deﬁned as age<35,<39,<45, and<50years)is associated with more aggressive pathology, including high-grade disease and positive margins(3,11-13,17, 19).Meijnen et al(11)reported that age<40years was corre-lated with a hazard ratio of8.7for local recurrence in the BCS setting.Consistent with studies of DCIS treated by mastectomy reporting that most recurrences were in women aged<60years(8, 14),the present series found that8of12recurrences occurred in women in this age group.However,other studies suggested that young age had no impact on LRR after BCS plus RT(6,20). Although the VNPI classiﬁes age<40years in the high-risk stratum,age alone was not statistically predictive of LRR in patients treated with BCS plus RT for DCIS on univariable or multivariable analysis(3).Further,the United Kingdom Co-ordinating Committee on Cancer Research andSwedish Fig. 1.Effect of age 40years on10-year locoregional recurrence.Volume- Number- 2012Outcomes postmastectomy for DCIS3randomized controlled trials comparing BCS with BCS plus RT for DCIS suggested that women aged <50years derived a lower absolute LRR risk reduction with RT (21,22).According to the present study’s ﬁndings and other available data,young age alone is not enough to justify a recommendation of PMRT.Further,the risks of PMRT,especially for young women,in particular second malignancy and coronary artery disease,may outweigh the small survival beneﬁt of postmastectomy radiation (likely <1%).To date,several studies support margin status as the most signiﬁcant predictor of LRR in patients with DCIS (12,14,17,23-26).In the present study,positive or close margins after mastec-tomy did not confer a statistically signiﬁcant increased risk of LRR (1.7%LRR with negative margins vs 4.6%LRR with close/positive margins).The deﬁnition of a negative margin varies greatly between institutions,from 1to 10mm.A pooled analysis of 4660patients from clinical trials of DCIS patients treated with BCS plus RT reported that a margin <2mm predicted for increased LRR.No increased risk of LRR was found in those with a margin between 2and 5mm (25).In the postmastectomy setting,Rashtian et al (14)examined 80patients (out of an initial 574cases)who had margins <10mm.The rates of LRR were 7.5%(6of 80)in the entire cohort and 16%(5of 31)in patients with margins <2mm.Of the 6recurrences,5(83%)had close margins ( 2mm).In contrast,Chan et al (23)analyzed 59post-mastectomy patients with close (<5mm)or positive margins and found no impact of margin status on recurrence.However,in that series the LRR rate was only 1.7%(1of 59).Skin-sparing mastectomy for DCIS may be associated with an increased risk of recurrence (23).Carlson et al (13)examined 223women treated with skin-sparing mastectomy for DCIS.The overall recurrence rate was 5.1%,which is 2-5times the baseline risk reported in several other retrospective studies.All recurrences had either close margins or high-grade disease,suggesting that the risk of recurrence was related to pathologic features rather than the type of mastectomy (13).Mastectomy type was not evaluated in this study because the prospective databases used did not record the type of mastectomy and the operative reports were not avail-able in all patient charts.High nuclear grade and comedonecrosis were not associated with greater risk of LRR in the present study (1.5%LRR for high grade vs 3%for grade 1/2).Multiple studies have shown these to be adverse pathologic features after BCS (3,6,14,23,27).In the Van Nuys series,the subgroup with both high nuclear grade and comedonecrosis had a disease-free survival of 65%(compared with 94%in patients without these 2factors).However,this subgroup analysis was based on only 21patients with both high nuclear grade and comedonecrosis (3).In the postmastectomy setting,high grade was correlated with a 3.3%risk of recurrence (1of 30patients)compared with a baseline risk of 1.7%(1of 59patients)(23).Variability in the reporting of pathologic grade likely accounted for these discrepancies.Even adjacent ducts on a single DCIS slide can be highly heterogeneous,making it difﬁcult to achieve consensus for grade assessment (28).The VNPI combines age,nuclear grade plus necrosis,margin status,and tumor size to predict LRR in patients with DCIS treated with BCS (17).Recently,Kelley et al (29)assigned VNPI scores to 496patients with DCIS treated with mastectomy.At 12years,the overall LRR was 2.2%,but patients with VNPI scores of 9-12had a higher LRR risk of 9.6%,compared with 0in those with scores of 4-8.None of the patients in Kelley’s series received PMRT (29).Distinct from these ﬁndings,the present study did not identify an association between the VNPI and LRR.In our cohort,there were no recurrences in the 29patients who had a VNPI score of 10-12.The VNPI was originally conceived for use in the BCS setting and as a decision-making guide for adjuvant RT or completion mastectomy.Although its application to the post-mastectomy setting is interesting,its validity remains untested in a prospective study.The present study raises many questions about the utility of postmastectomy radiation in the DCIS setting.Even in the group with the highest LRR (age 40years),the risk of recurrence was <10%(7.0%).The low baseline risk of recurrence likely precludes the study of this question in a randomized,controlled trial.It is also difﬁcult to draw deﬁnitive conclusions in the retrospective setting.Our study was limited by both a very low recurrence rate (12of 646)and missing data.The data sources captured all cases of pure DCIS diagnosed in British Columbia during the study era (n Z 2805).Treatment information was only available for cases referred to the BC Cancer Agency at diagnosis or recurrence and most cases within the DCIS database who were not referred but who were initially treated with mastectomy.Among the study population,646of 2805patients withDCISOwen et al.International Journal of Radiation Oncology Biology Physics4were not referred to a cancer center for management,and it is likely that some proportion of this group would have had mastectomy as an initial treatment(eg,after an initial lumpec-tomy/biopsy)and not be captured in this cohort.For this analysis, we were unable to determine how many of these cases not referred to one of the provincial cancer centers had mastectomies and were not included in this analysis.ConclusionsThe present study conﬁrmed that oncologic outcomes in postmastectomy DCIS patients were excellent.A subgroup with an increased>10%risk for LRR was not identiﬁed. Routine use of PMRT is not justiﬁed.Postmastectomy RT could offer a modest reduction in LRR in very young women that needs to be carefully weighed against the potential side effects.References1.British Columbia Cancer Agency.BC Cancer Registry(Nov2007).Available at:http://www.bccancer.bc.ca/HPI/CancerStatistics/FF/ cancercases.htm.Accessed January31,2011.2.van Steenbergen LN,V oogd AC,Roukema JA,et al.Screening causedrising incidence rates of ductal carcinoma in situ of the breast.Breast Cancer Res Treat2009;115:181-183.3.Silverstein MJ,Barth A,Poller DN,et al.Ten-year results comparingmastectomy to excision and radiation therapy for ductal carcinoma in situ of the breast.Eur J Cancer1995;31A:1425-1427.4.Polgar C,Kahan Z,Orosz Z,et al.The role of radiotherapy in theconservative treatment of ductal carcinoma in situ of the breast.Pathol Oncol Res2008;14:179-192.5.Bijker N,Meijnen P,Peterse JL,et al.Breast-conserving treatmentwith or without radiotherapy in ductal carcinoma-in-situ:Ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial10853d a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group.J Clin Oncol2006;24:3381-3387.6.Boyages J,Delaney G,Taylor R.Predictors of local recurrence aftertreatment of ductal carcinoma in situ:A meta-analysis.Cancer1999;85:616-628.7.Fisher B,Anderson S,Redmond CK,et al.Reanalysis and results after12years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer.N Engl J Med1995;333:1456-1461.8.Kim JH,Tavassoli F,Haffty BG.Chest wall relapse after mastectomyfor ductal carcinoma in situ:a report of10cases with a review of the literature.Cancer J2006;12:92-101.9.Burstein HJ,Polyak K,Wong JS,et al.Ductal carcinoma in situ of thebreast.N Engl J Med2004;350:1430-1441.10.Newman LA.Local control of ductal carcinoma in situ based on tumorand patient characteristics:The surgeon’s perspective.J Natl Cancer Inst Monogr2010;2010:152-157.11.Meijnen P,Oldenburg HS,Peterse JL,et al.Clinical outcome afterselective treatment of patients diagnosed with ductal carcinoma in situ of the breast.Ann Surg Oncol2008;15:235-243.12.Vargas C,Kestin L,Go N,et al.Factors associated with local recur-rence and cause-speciﬁc survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastec-tomy.Int J Radiat Oncol Biol Phys2005;63:1514-1521.13.Carlson GW,Page A,Johnson E,et al.Local recurrence of ductalcarcinoma in situ after skin-sparing mastectomy.J Am Coll Surg2007;204:1074-1078.14.Rashtian A,Iganej S,Amy Liu IL,et al.Close or positive marginsafter mastectomy for DCIS:Pattern of relapse and potential indica-tions for radiotherapy.Int J Radiat Oncol Biol Phys2008;72:1016-1020.15.Wai ES,Lesperance ML,Alexander CS,et al.Predictors of localrecurrence in a population-based cohort of women with ductal carci-noma in situ treated with breast conserving surgery alone.Ann Surg Oncol2011;18:119-124.16.Olivotto IA,Kan L,d’Yachkova Y,et al.Ten years of breast screeningin the Screening Mammography Program of British Columbia,1988-97.J Med Screen2000;7:152-159.17.Silverstein MJ.The University of Southern California/Van Nuysprognostic index for ductal carcinoma in situ of the breast.Am J Surg 2003;186:337-343.18.Li CI,Malone KE,Saltzman BS,et al.Risk of invasive breast carci-noma among women diagnosed with ductal carcinoma in situ and lobular carcinoma in situ,1988-2001.Cancer2006;106:2104-2112.19.Goldstein NS,Vicini FA,Kestin LL,et al.Differences in the patho-logic features of ductal carcinoma in situ of the breast based on patient age.Cancer2000;88:2553-2560.20.Turaka A,Freedman GM,Li T,et al.Young age is not associated withincreased local recurrence for DCIS treated by breast-conserving surgery and radiation.J Surg Oncol2009;100:25-31.Volume- Number- 2012Outcomes postmastectomy for DCIS521.Houghton J,George WD,Cuzick J,et al.Radiotherapy and tamoxifenin women with completely excised ductal carcinoma in situ of the breast in the UK,Australia,and New Zealand:Randomised controlled ncet2003;362:95-102.22.Holmberg L,Garmo H,Granstrand B,et al.Absolute risk reductionsfor local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast.J Clin Oncol2008;26:1247-1252.23.Chan LW,Rabban J,Hwang ES,et al.Is radiation indicated in patientswith ductal carcinoma in situ and close or positive mastectomy margins?Int J Radiat Oncol Biol Phys2011;80:25-30.24.Monteau A,Sigal-Zafrani B,Kirova YM,et al.Ductal carcinoma in situof the breast with close or focally involved margins following breast-conserving surgery:Treatment with reexcision or radiotherapy with increased dosage.Int J Radiat Oncol Biol Phys2009;75:1021-1028.25.Dunne C,Burke JP,Morrow M,et al.Effect of margin status on localrecurrence after breast conservation and radiation therapy for ductal carcinoma in situ.J Clin Oncol2009;27:1615-1620.26.Meijnen P,Gilhuijs KG,Rutgers EJ.The effect of margins on theclinical management of ductal carcinoma in situ of the breast.J Surg Oncol2008;98:579-584.27.Bellamy CO,McDonald C,Salter DM,et al.Noninvasive ductalcarcinoma of the breast:The relevance of histologic categorization.Hum Pathol1993;24:16-23.ler NA,Chapman JA,Qian J,et al.Heterogeneity between ducts ofthe same nuclear grade involved by duct carcinoma in situ(DCIS)of the breast.Cancer Inform2010;9:209-216.29.Kelley L,Silverstein M,Guerra L.Analyzing the risk of recurrenceafter mastectomy for DCIS:A new use for the USC/Van Nuys Prog-nostic Index.Ann Surg Oncol2011;18:459-462.Owen et al.International Journal of Radiation Oncology Biology Physics 6。