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False-Negative Interpretation of Breast Sentinel Lymph Node Touch Preps: Analysis of the Causes with Suggestions to Improve Diagnostic Accuracy 乳房前哨淋巴结触诊假阴性解释:原因分析及提高诊断准确率的建议
Pub Date : 2014-01-01 DOI: 10.7156/NAJMS.2014.0702068
Frank Chen, D. Hicks, M. Nava, R. Cheney
Sentinel lymph node (SLN) biopsy has become widely accepted as an important procedure in staging breast cancer. False-negative results of touch prep (TP) examination at time of SLN biopsy requires additional surgery, delaying treatment and increasing cost. Therefore, we have analyzed our experience with false-negative interpretation on SLN TP’s. Eight-hundred and three consecutive SLN biopsies from 2003 to 2005 were obtained from the pathology archive of Roswell Park Cancer Institute. The intraoperative consultation results were correlated with the final diagnoses.  Twenty-five SLN intraoperative consultations had false-negative TP’s [false-negative rate = 3.1% (25/803), including 9 metastatic lobular carcinomas and 16 metastatic ductal carcinomas]. These cases were re-evaluated by 3 pathologists independently, and the metastases in the SLN sections were confirmed by positive cytokeratin staining.  Size of the metastatic focus, nuclear grade and the adequacy of TP’s were analyzed with regard to the cause of false-negative results. On re-screening of TP’s, we found that rare tumor cells of low nuclear grade were identified on 28% (7/25) of the TP’s (3 metastatic lobular carcinomas and 4 metastatic ductal carcinomas). In the remaining 72% (18/25) of TP’s, re-screening revealed no evidence of tumor.  Evaluation of these TP’s demonstrated that 50% (9/18) were unsatisfactory for evaluation or limited by scant cellularity. While cases that remained negative on re-screening tended to have smaller measured foci of tumor in the SLN (Average 0.65 mm vs. 0.94 mm from cases that were positive on re-screening), there was considerable overlap between these two groups. In conclusion, TP’s with scant cellularity, unsatisfactory TP’s and failure to identify tumor cells with low nuclear grade were found to significantly contribute to false-negative interpretations. We suggest that an additional TP or frozen section may be necessary if the cellularity of the initial TP is limited.  Correlation with the original core biopsy may be of value to help in identifying cancer cells of low nuclear grade.
前哨淋巴结(SLN)活检已被广泛接受为乳腺癌分期的重要程序。SLN活检时接触准备(TP)检查的假阴性结果需要额外的手术,延迟治疗并增加费用。因此,我们分析了我们在SLN TP上的假阴性解释的经验。从2003年到2005年,从Roswell Park癌症研究所的病理档案中获得了883例连续的SLN活检。术中会诊结果与最终诊断结果相关。术中SLN会诊有25例TP假阴性[假阴性率3.1%(25/803),其中转移性小叶癌9例,转移性导管癌16例]。这些病例由3名病理学家独立重新评估,细胞角蛋白染色阳性证实了SLN切片的转移。分析了转移灶的大小、核分级和TP的充分性对假阴性结果的影响。在TP的重新筛查中,我们发现28%(7/25)的TP中发现了罕见的低核级肿瘤细胞(3例转移性小叶癌和4例转移性导管癌)。其余72%(18/25)的TP患者,重新筛查未发现肿瘤。对这些TP的评价表明,50%(9/18)的评价不满意或受到细胞缺乏的限制。虽然重新筛查呈阴性的病例往往在SLN中有较小的肿瘤灶(平均0.65 mm对0.94 mm),但这两组之间存在相当大的重叠。总之,缺乏细胞性的TP,不满意的TP和不能识别低核分级的肿瘤细胞是导致假阴性解释的重要原因。我们建议,如果初始TP的细胞数量有限,可能需要额外的TP或冷冻切片。与原始核心活检的相关性可能有助于识别低核级别的癌细胞。
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引用次数: 0
Clinical Monitoring of Chronic Hepatitis C Based on its Natural History and Therapy. 根据慢性丙型肝炎的自然病史和治疗方法对其进行临床监测。
Douglas L Nguyen, Ke-Qin Hu

Hepatitis C virus (HCV) infection is a major public health problem and a leading cause of chronic liver disease. Chronic HCV infection often follows a progressive course over years and can result in cirrhosis, hepatocellular carcinoma, and need for liver transplantation. In the United States alone, the estimated prevalence of HCV infection is up to 5.1 million persons. The optimal approach to detecting HCV infection is to screen persons for possible history of risks of exposure to virus and to test those selected individuals with risk factors. Both host and viral factors may be important contributors to the natural history of HCV. Currently, effective pharmacologic therapy are available to induce sustained virologic response (SVR) or virologic "cure," which results in improved morbidity and mortality. Patient education before treatment is essential and should include a full discussion of potential side effects. It is important to work collaboratively and closely with patients to ensure early recognition of adverse events and to effectively manage them in order to ensure treatment compliance. This paper provides a thorough overview on screening for the diagnosis, clinical management, and treatment indications and contraindications for chronic hepatitis C.

丙型肝炎病毒(HCV)感染是一个重大的公共卫生问题,也是慢性肝病的主要病因。慢性丙型肝炎病毒感染通常会持续数年,可导致肝硬化、肝细胞癌和肝移植。仅在美国,估计感染 HCV 的人数就高达 510 万。检测 HCV 感染的最佳方法是筛查可能有接触病毒风险的人群,并对具有风险因素的特定人群进行检测。宿主和病毒因素都可能是影响 HCV 自然病史的重要因素。目前,有效的药物疗法可诱导持续病毒学应答(SVR)或病毒学 "治愈",从而改善发病率和死亡率。治疗前的患者教育至关重要,其中应包括对潜在副作用的充分讨论。重要的是要与患者密切合作,确保尽早识别不良反应并进行有效管理,以确保治疗依从性。本文全面概述了慢性丙型肝炎的诊断筛查、临床管理、治疗适应症和禁忌症。
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引用次数: 0
Non-Invasive Prenatal Diagnosis: A Comparison of Cell Free Fetal DNA (cffDNA) Based Screening and Fetal Nucleated Red Blood Cell (fnRBC) Initiated Testing 无创产前诊断:基于游离细胞胎儿DNA (cffDNA)筛查和胎儿有核红细胞(fnRBC)启动测试的比较
Pub Date : 2013-10-30 DOI: 10.7156/NAJMS.2013.0604194
Zhi-yong Xu, Jiansheng Xie, Jinlai Meng, Peining Li, Xinghua Pan, Qinghua Zhou
Current prenatal diagnosis uses non-invasive procedures of maternal serum screening and ultrasound exam to evaluate the risk of chromosomal abnormalities and invasive procedures of chorionic villus sampling and amniocentesis for the diagnosis of cytogenomic abnormalities and gene mutations. The discovery of cell free fetal DNA (cffDNA) in maternal blood prompted the application of massive parallel sequencing to screen fetal aneuploidies. The multi-center large-scale validation of cffDNA based prenatal screening has resulted in rapid integration of this close-to-diagnostic non-invasive procedure into clinical application. Further improvement of this approach could lead to the screening of pathogenic copy number variants and known disease-causing gene mutations. The success from cffDNA fuels efforts in isolating circulating fetal nucleated red blood cells (fnRBCs) for direct non-invasive prenatal testing of fetal genetic disorders. Various isolation and enrichment methods based on the physical and biologic features of the fnRBCs have been developed but the analytic and clinical validities have not yet been established. The cffDNA based prenatal screening has significantly reduced unnecessary invasive procedures. Future breakthrough on fnRBC initiated prenatal testing will further shift the paradigm toward non-invasive prenatal diagnosis.     [N A J Med Sci. 2013;6(4):194-199.   DOI: 10.7156/najms.2013.0604194]
目前的产前诊断采用无创的方法如母体血清筛查和超声检查来评估染色体异常的风险,采用有创的方法如绒毛膜绒毛取样和羊膜穿刺术来诊断细胞基因组异常和基因突变。母体血液中游离细胞胎儿DNA (cffDNA)的发现促使大量平行测序技术应用于筛选胎儿非整倍体。基于cffDNA的产前筛查的多中心大规模验证导致这种接近诊断的非侵入性程序快速整合到临床应用中。这种方法的进一步改进可能导致致病拷贝数变异和已知的致病基因突变的筛选。cfdna的成功推动了分离循环胎儿有核红细胞(fnrbc)用于胎儿遗传疾病的直接无创产前检测的努力。基于fnrbc的物理和生物学特性,已经开发了各种分离和富集方法,但尚未建立分析和临床有效性。基于cffDNA的产前筛查大大减少了不必要的侵入性程序。未来在fnRBC发起的产前检测方面的突破将进一步将范式转向无创产前诊断。[J] .中华医学杂志,2013;6(4):194-199。DOI: 10.7156 / najms.2013.0604194]
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引用次数: 8
Opportunities and Challenges in Molecular Genetic Testing in China: The Experience of an Academic Center for Clinical Molecular Medicine 中国分子基因检测的机遇与挑战:临床分子医学学术中心的经验
Pub Date : 2013-10-30 DOI: 10.7156/NAJMS.2013.0604213
Lin Zou, X. Chen, Xiaoyan He, L. Bao
Molecular genetic testing and molecular pathology are relatively new but rapidly growing fields in China. This article reports on the experience of providing molecular genetic testing at the Center for Clinical Molecular Medicine (CCMM) of Chongqing Medical University in China. This center is the first of such centers in the southwestern region of China and implements a spectrum of genetic tests on constitutional cytogenetics, oncology cytogenetics, molecular cytogenetics, molecular genetics, molecular oncology, metabolic genetics, and newborn screening. The annual test volume had a 78-fold increase in the past five years and reached approximately 380,000 tests in 2012. This tremendous growth reflects both great opportunities and challenges for China’s healthcare system. Some of the challenges such as the lack of a medical genetics professionals and qualified training programs for clinical geneticists, laboratory specialists and genetic counselors are discussed.
分子基因检测和分子病理学在中国是相对较新的但发展迅速的领域。本文报道了重庆医科大学临床分子医学中心(CCMM)提供分子基因检测的经验。该中心是中国西南地区第一家这样的中心,实施了体质细胞遗传学、肿瘤细胞遗传学、分子细胞遗传学、分子遗传学、分子肿瘤学、代谢遗传学和新生儿筛查等一系列基因检测。在过去五年中,年检测量增长了78倍,2012年达到约38万次。这种巨大的增长反映了中国医疗体系面临的巨大机遇和挑战。讨论了一些挑战,如缺乏医学遗传学专业人员和临床遗传学家、实验室专家和遗传咨询师的合格培训计划。
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引用次数: 3
Fragile X Syndrome in China 中国的脆性X综合征
Pub Date : 2013-07-31 DOI: 10.7156/NAJMS.2013.0604181
R. Duan, K. Garber, P. Jin
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID), and the leading monogenic cause of autism spectrum disorders. The FXS cases in China were first reported in 1984, and effort has been made to improve the wellbeing of FXS patients. However, the general Chinese population is unfamiliar with FXS due to the limited public education. Even among those with medical training, there is a lack of awareness. Here our review aims to provide basic information on FXS, introduce the clinical aspects of FXS in China, and outline future research and policy recommendations that may in the future improve FXS genetic testing and counselor training in the Chinese health system.  [N A J Med Sci. 2013;6(4):181-185.   DOI: 10.7156/najms.2013.0604181]
脆性X染色体综合征(FXS)是遗传性智力障碍(ID)最常见的形式,也是自闭症谱系障碍的主要单基因原因。中国早在1984年就报告了FXS病例,并一直在努力改善FXS患者的福祉。然而,由于公众教育的限制,一般中国人对FXS并不熟悉。即使是受过医学训练的人,也缺乏这方面的认识。本文旨在提供FXS的基本信息,介绍FXS在中国的临床情况,并概述未来的研究和政策建议,以改进中国卫生系统中FXS基因检测和咨询师培训。[J] .中华医学杂志,2013;6(4):181-185。DOI: 10.7156 / najms.2013.0604181]
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引用次数: 2
Stability and Reproducibility of the Measurement of Plasma Nitrate in Large Epidemiologic Studies. 大型流行病学研究中血浆硝酸盐测量的稳定性和可重复性。
Yushan Wang, Mary K Townsend, A Heather Eliassen, Tianying Wu

Inorganic nitrate has emerged as a therapeutic agent for cardiovascular disease; however, nitrate can also metabolize to carcinogenic nitrosamines under pathologic conditions. Few large epidemiologic studies have examined circulating levels of nitrate in relation to cardiovascular disease and cancer. Data on the validity of nitrate measurement in blood samples collected in typical epidemiologic settings are needed before nitrate can be evaluated as an exposure in large epidemiologic studies. We measured plasma levels of nitrate in three pilot studies to evaluate its laboratory variability, stability with delayed processing, and reproducibility over time among women from the Nurses' Health Study and healthy female volunteers. Laboratory variability of nitrate levels was fairly low, with a coefficient variation (CV) of 7%. Plasma nitrate levels in samples stored as whole blood on ice for up to 48 hrs before processing were very stable; the overall intra-class correlation (ICC) from 0 to 48 hours was 0.89 (95%CI, 0.70-0.97). The within-person reproducibility over a one-year period was modest, with an ICC of 0.49 (95% CI, 0.33- 0.94). Our results indicate that measurement of nitrate in plasma is reliable and stable in blood samples with delayed processing up to 48 hours. Within-person reproducibility was modest but data from this study can be used for measurement error correction in subsequent analyses. The measurement of nitrate cannot be widely used in epidemiologic research without the documentation of its stability and reproducibility.

无机硝酸盐已成为心血管疾病的治疗剂;然而,在病理条件下,硝酸盐也可代谢为致癌物亚硝胺。很少有大型流行病学研究调查了血液中硝酸盐水平与心血管疾病和癌症的关系。在大型流行病学研究中评估硝酸盐暴露之前,需要在典型流行病学环境中收集的血液样本中硝酸盐测量的有效性数据。我们在三个试点研究中测量血浆硝酸盐水平,以评估其实验室变异性,延迟处理的稳定性,以及护士健康研究妇女和健康女性志愿者随时间的可重复性。硝酸盐水平的实验室变异性相当低,变异系数(CV)为7%。在处理前作为全血在冰上保存48小时的样品中血浆硝酸盐水平非常稳定;从0到48小时的总体类内相关性(ICC)为0.89 (95%CI, 0.70-0.97)。在一年的时间内,人内重现性一般,ICC为0.49 (95% CI, 0.33- 0.94)。我们的研究结果表明,在延迟处理长达48小时的血液样本中,血浆中硝酸盐的测量是可靠和稳定的。人体内重现性一般,但本研究的数据可用于后续分析中的测量误差校正。如果没有稳定性和可重复性的记录,硝酸盐的测量就不能广泛应用于流行病学研究。
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引用次数: 0
Challenges and Needs of Chinese and Korean American Breast Cancer Survivors: In-Depth Interviews. 华裔和韩裔美国人乳腺癌幸存者的挑战和需求:深度访谈。
Pub Date : 2013-02-02 DOI: 10.7156/najms.2013.0601001
Sunmin Lee, Lu Chen, Grace X Ma, Carolyn Y Fang, Youngsuk Oh, Lynn Scully

Breast cancer incidence and the number of breast cancer survivors have been rapidly increasing among Chinese and Korean women in the United States. However, few data are available regarding quality of life in Asian American breast cancer survivors. This qualitative study aims to describe Asian American women's perceptions of quality of life and their breast cancer experiences. In-depth interviews with four Chinese and five Korean American breast cancer survivors and three oncologists were conducted in Chinese, Korean, or English. Interviews were recorded and transcripts were translated into English. Qualitative analyses were performed by two independent coders and then discussed and agreed upon by the research team. The respondents reported that the breast cancer experience had affected various domains of quality of life, but women reported having limited resources with which to cope effectively. Depression, anxiety, and stress were commonly reported, but women rarely discussed these issues with family and friends or sought professional help. As immigrants, women's loneliness and a lack of social support and culturally relevant resources seemed to be major barriers to maintaining good quality of life. Women also expressed interest in learning more about alternative therapies and relaxation skills. These findings can be used to help inform the development of a culturally appropriate intervention for Asian American breast cancer survivors. Future programs may provide information in women's native languages to teach skills to cope with stress and anxiety, increase women's self-efficacy within the context of their cultural background, and enhance social support among women from the same ethnic group.

在美国的中国和韩国女性中,乳腺癌的发病率和乳腺癌幸存者的数量一直在迅速增加。然而,很少有关于亚裔美国乳腺癌幸存者生活质量的数据。本定性研究旨在描述亚裔美国女性对生活质量的看法和她们患乳腺癌的经历。对4名中国和5名韩裔美国乳腺癌幸存者和3名肿瘤学家进行了深入访谈,访谈用中文、韩语和英语进行。采访被记录下来,笔录被翻译成英文。定性分析由两个独立的编码员进行,然后由研究团队讨论并达成一致。受访者报告说,乳腺癌经历影响了生活质量的各个领域,但妇女报告说,她们有效应对的资源有限。抑郁、焦虑和压力是常见的报告,但女性很少与家人和朋友讨论这些问题或寻求专业帮助。作为移民,妇女的孤独和缺乏社会支持和与文化有关的资源似乎是维持良好生活质量的主要障碍。女性还表示有兴趣学习更多的替代疗法和放松技巧。这些发现可以用来帮助为亚裔美国乳腺癌幸存者制定文化上适当的干预措施。未来的项目可能会用女性的母语提供信息,教授她们应对压力和焦虑的技能,提高女性在其文化背景下的自我效能感,并增强来自同一民族的女性的社会支持。
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引用次数: 55
Developing a Predictive Gene Classifier for Autism Spectrum Disorders Based upon Differential Gene Expression Profiles of Phenotypic Subgroups. 基于表型亚群差异基因表达谱建立自闭症谱系障碍预测基因分类器。
Pub Date : 2013-01-01 DOI: 10.7156/najms.2013.0603107
Valerie W Hu, Yinglei Lai

Autism spectrum disorders (ASD) are neurodevelopmental disorders which are currently diagnosed solely on the basis of abnormal stereotyped behavior as well as observable deficits in communication and social functioning. Although a variety of candidate genes have been identified on the basis of genetic analyses and up to 20% of ASD cases can be collectively associated with a genetic abnormality, no single gene or genetic variant is applicable to more than 1-2 percent of the general ASD population. In this report, we apply class prediction algorithms to gene expression profiles of lymphoblastoid cell lines (LCL) from several phenotypic subgroups of idiopathic autism defined by cluster analyses of behavioral severity scores on the Autism Diagnostic Interview-Revised diagnostic instrument for ASD. We further demonstrate that individuals from these ASD subgroups can be distinguished from nonautistic controls on the basis of limited sets of differentially expressed genes with a predicted classification accuracy of up to 94% and sensitivities and specificities of ~90% or better, based on support vector machine analyses with leave-one-out validation. Validation of a subset of the "classifier" genes by high-throughput quantitative nuclease protection assays with a new set of LCL samples derived from individuals in one of the phenotypic subgroups and from a new set of controls resulted in an overall class prediction accuracy of ~82%, with ~90% sensitivity and 75% specificity. Although additional validation with a larger cohort is needed, and effective clinical translation must include confirmation of the differentially expressed genes in primary cells from cases earlier in development, we suggest that such panels of genes, based on expression analyses of phenotypically more homogeneous subgroups of individuals with ASD, may be useful biomarkers for diagnosis of subtypes of idiopathic autism.

自闭症谱系障碍(ASD)是一种神经发育障碍,目前仅根据异常的刻板行为以及可观察到的沟通和社会功能缺陷来诊断。尽管在遗传分析的基础上已经确定了多种候选基因,并且高达20%的ASD病例可能与遗传异常有关,但没有任何单一基因或遗传变异适用于超过1- 2%的一般ASD人群。在本报告中,我们将分类预测算法应用于特发性自闭症的几个表型亚组的淋巴母细胞样细胞系(LCL)的基因表达谱,这些亚组是由自闭症诊断访谈-修订的自闭症诊断工具上的行为严重程度评分的聚类分析定义的。我们进一步证明,基于有限的差异表达基因集,基于留一验证的支持向量机分析,这些ASD亚群的个体可以与非自闭症对照组区分开来,预测分类准确率高达94%,敏感性和特异性约为90%或更高。通过高通量定量核酸酶保护试验,对来自一个表型亚群的个体和一组新的对照组的一组新的LCL样本进行“分类”基因子集的验证,总体分类预测准确率为82%,灵敏度为90%,特异性为75%。虽然还需要更大的队列验证,而且有效的临床翻译必须包括来自早期发育病例的原代细胞中差异表达基因的确认,但我们认为,基于表型上更均匀的ASD个体亚群的表达分析,这种基因小组可能是诊断特发性自闭症亚型的有用生物标志物。
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引用次数: 31
Genetic Counseling Training in China: A Pilot Program at Fudan University 中国遗传咨询培训:复旦大学的试点项目
Pub Date : 2013-01-01 DOI: 10.7156/NAJMS.2013.0604221
Y. An, Hongyan Chen, Li Jin, Bai-Lin Wu, D. Lu
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引用次数: 4
Board Certification Systems for Clinical Geneticists and Genetic Counselors in Taiwan 台湾临床遗传学家及遗传咨询师之委员会认证制度
Pub Date : 2013-01-01 DOI: 10.7156/NAJMS.2013.0604223
A. Tsai
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引用次数: 2
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