永利402图解 | 单克隆免疫性球蛋白相关性肾病(进阶版)

后1个月有战友已对该文实行总论翻译,个人认为各论部分也格外值得阅读与收藏,特整理为多个表格,便于翻看。

DCIS医疗去不掉放射性治疗

骨干质量

  • 长度
    永利402 1

    Azad A A, Volik S V, Wyatt A W, et al. Androgen Receptor Gene
    Aberrations in Circulating Cell-Free DNA: Biomarkers of
    Therapeutic Resistance in Castration-Resistant Prostate
    Cancer.[J]. Journal of Urology, 2015, 194(3):704-704.

永利402 2
在1陆7bp左右(对应染色小体长度)有三个峰,并且其余的峰有着拾.5bp的周期波动,对应着核小体宗旨DNA的螺距

Snyder M W, Kircher M, Hill A J, et al. Cell-free DNA comprises an in
vivo nucleosome footprint that informs its tissues-of-origin[J].
Cell, 2016, 164(1-2):57.

  • 生物学来源
  1. 凋亡和坏死

    Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, et
    al. (2001) DNA fragments in the blood plasma of cancer patients:
    quantitations and evidence for their origin from apoptotic and
    necrotic cells Cancer Res 61:1659–65. pmid:11245480
    Giacona M B, Ruben G C, Iczkowski K A, et al. Cell-free DNA in
    human blood plasma: length measurements in patients with
    pancreatic cancer and healthy controls[J]. Pancreas, 1998,
    17(1):89.

  2. 移植物也许胎儿的游离DNA(参考文献见下)

  3. 独立自己作主激活的DNA的获释

    Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P (2001)
    About the possible origin and mechanism of circulating DNA
    apoptosis and active DNA release. Clin Chim Acta 313:139–42.
    pmid:11694251

  • 应用
  1. 胚胎的DNA会游离到孕妇的血流中,怀男孩的产妇血液能够检查评定到Y染色体,还可用来产前检查测试,2一和1八三体

    Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman
    CWG,et al. Presence of fetal DNA in maternal plasma and serum.
    Lancet
    1997;350:485–7
    Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das
    AF,et al. DNA sequencing versus standard prenatal aneuploidy
    screening.N Engl J Med 2014;370:799–808

  2. 器官移植免疫性排斥产生的细胞长逝,DNA会释放到血液中,由此用于器官移植状态的监察

    Beck J, Oellerich M, Schulz U, Schauerte V, Reinhard L, Fuchs U,
    et al.Donor-derived cell-free DNA is a novel universal biomarker
    for allograft rejection in solid organ transplantation. Transplant
    Proc 2015;47:2400–3

  3. cfDNA浓度与外伤、口干的摧残程度有关

    Butt AN, Swaminathan R. Overview of circulating nucleic acids in
    plasma serum. Ann N Y Acad Sci 2008;1137:236–42

  4. 高浓度cfDNA也用于ICU病逝的展望,也可用来预测脓毒症和脓毒性休克,无菌性炎症,心肌梗死和无印象学结果的脑蛛网膜炎病人患病境况。

    Volik S, Alcaide M, Morin R D, et al. Cell-free DNA (cfDNA):
    Clinical Significance and Utility in Cancer Shaped By Emerging
    Technologies[J]. Molecular Cancer Research Mcr, 2016:898-908.

  5. 肿瘤来源的cfDNA,能够发掘肿瘤相关的气象一新、杂合子缺失(LOH)、基因扩大与增添、癌病毒DNA、抑癌基因运维子区的超异丁烯化,因而得以兑以后无创条件下商讨肿瘤DNA

    Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M.
    Neoplastic characteristics of the DNA found in the plasma of
    cancer patients.
    Oncology 1989;46:318–22
    Chen XQ, Stroun M, Magnenat JL, Nicod LP, Kurt AM, Lyautey J, et
    al.Microsatellite alterations in plasma DNA of small cell lung
    cancer patients.
    Nat Med 1996;2:1033–5
    Chiang P-W, Beer DG, Wei W-L, Orringer MB, Kurnit DM. Detection
    oferbB-2 amplifications in tumors and sera from esophageal
    carcinoma
    patients. Clin Cancer Res 1999;5:1381–6
    Mutirangura A, Pornthanakasem W, Theamboonlers A, Sriuranpong
    V,Lertsanguansinchi P, Yenrudi S, et al. Epstein-Barr viral DNA in
    serum of
    patients with nasopharyngeal carcinoma. Clin Cancer Res
    1998;4:665–9
    Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB,
    HermanJG. Detection of aberrant promoter hypermethylation of tumor
    suppressor
    genes in serum DNA from non-small cell lung cancer patients.
    Cancer Res1999;59:67–70.

  6. 核小体在TSS区是还是不是攻陷,影响cfDNA的纵深,因而得以用来估摸基因的说明景况

    Ulz P, Thallinger G G, Auer M, et al. Inferring expressed genes by
    whole-genome sequencing of plasma DNA.[J]. Nature Genetics,
    2016, 48(10):1273.

  1. 48: 第 258 – 273 页.[3]. Lund, T.M., et al., Effect of morning
    versus evening intake of simvastatin on the serum cholesterol level in
    patients with coronary artery disease. Am J Cardiol, 2002. 90: p. 784 –
    6.[4]. Wallace, A., D. Chinn and G. Rubin, Taking simvastatin in the
    morning compared with in the evening: randomised controlled trial. BMJ,
  2. 327: p. 788.[5]. Illingworth, D.R., Comparative efficacy of once
    versus twice daily mevinolin in the therapy of familial
    hypercholesterolemia. Clin Pharmacol Ther, 1986. 40: p. 338 – 43.[6].
    Hunninghake, D.B., et al., Efficacy and safety of pravastatin in
    patients with primary hypercholesterolemia. II. Once-daily versus
    twice-daily dosing. Atherosclerosis, 1990. 85: p. 219 – 27.[7]. Muck,
    W., et al., Pharmacokinetics of cerivastatin when administered under
    fasted and fed conditions in the morning or evening. Int J Clin
    Pharmacol Ther, 2000. 38: p. 298 – 303.[8]. Scharnagl, H., et al.,
    Efficacy and safety of fluvastatin-extended release in
    hypercholesterolemic patients: morning administration is equivalent to
    evening administration. Cardiology, 2006. 106: p. 241 – 8.[9]. Fauler,
    G., et al., Time-of-intake (morning versus evening) of extended-release
    fluvastatin in hyperlipemic patients is without influence on the
    pharmacodynamics (mevalonic acid excretion) and pharmacokinetics. Int J
    Clin Pharmacol Ther, 2007. 45: p. 328 – 34.[10]. Yi, Y.J., et al.,
    Comparison of the efficacy and safety profile of morning administration
    of controlled-release simvastatin versus evening administration of
    immediate-release simvastatin in chronic kidney disease patients with
    dyslipidemia. Clin Ther, 2014. 36: p. 1182 – 90.[11]. Cilla, D.J., et
    al., Pharmacodynamic effects and pharmacokinetics of atorvastatin after
    administration to normocholesterolemic subjects in the morning and
    evening. J Clin Pharmacol, 1996. 36: p. 604 – 9.[12]. Martin, P.D.,
    P.D. Mitchell and D.W. Schneck, Pharmacodynamic effects and
    pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin,
    after morning or evening administration in healthy volunteers. Br J Clin
    Pharmacol, 2002. 54: p. 472 – 7.[13]. 查锡良. 生化.
    东京(Tokyo):人卫出版社,20一三.[14]. UpToDate 临床决策数据库
    www.uptodate.com

13、 Ravindran A, Fervenza FC, Smith RJ, Sethi
S:C3 glomerulopathy associated with
monoclonalIg: A distinct subtype. Kidney Intdoi:
10.1016/j.kint.2018.01.037.

丹娜法伯医院的考试提供了另一份数据。该考试纳入肿瘤大小<2.5cm、肿瘤边缘阴性≥一cm、一半级DCIS术后伤者。在这一个低风险伤者中,8年的片段复发率>①3%,在那之中三分之壹的伤者是浸透性复发。

定义

Circulating free DNA or Cell free DNA
(cfDNA):循环游离DNA或许细胞游离DNA,释放到血浆中的降解的DNA片段。

她汀类药物在神经科和心产科可谓是到处开花。调整血脂、下降心脑血管疾患的发病率是它们的本分,同时又独具各个美妙的兼顾:抗氧化、缓和炎症、抑制心室重构、改进COPD 结局、下降胆管扩张症发病率,以致下落表皮囊肿和认识障碍的高危机
[1]。可谓多才多艺。201肆 年中中原人民共和国缺血性卒中 / TIA
二级防备汛抗旱指挥部南建议:对于非心源性缺血性脑卒中 / TIA
伤者,无论是或不是伴有任何动脉粥样硬化证据,均推荐给予高强度他汀类药物长时间诊治,以减弱脑卒二月心血管事件危机。[2]所谓「高强度他汀医疗」是指阿托伐他汀
40~80 mg/d 或瑞舒伐他汀 20~40
mg/d,由此可见他汀们在神经科使用面之广、量之大。但据了然,从小诊所到大三甲,从心男科到神经科,绝大诸多先生都习于旧贯给予他汀们夜间服用;只要有它们出现的地点,便顺手勾上
qn。这么做到底有没有道理呢?为何需求夜间服用?那将在从他汀的药理功用讲起。人体内胆固醇合成是个拔尖复杂的工程,轻易说分叁等第:甲羟戊酸的合成、鲨烯的合成、胆固醇的合成。在那之中第3阶段如下:乙酰
CoA 经过 三 步酶促反应合成甲羟戊酸,当中 H名爵-CoA
还原酶是关键酶,也是成套胆固醇合成的重大酶。而她汀类药物就是壹种选用性、竞争性的
HMG-CoA 还原酶抑制剂,它们通过竞争性抑制 HMG-CoA
还原酶来压制整个胆固醇的合成。胆固醇的合成首要在肝,而肝 HMG-CoA
还原酶自有其天性;它有昼夜节律,活性在上午低于,半夜最高。所以身体内胆固醇的合成也有节律性,早上最少,半夜最多。倘诺夜间咽下他汀,血浆消除半衰期在数个小时,半夜时刚好达到血药浓度高峰,能够起到极品效果。那上头业已有多项切磋,对于辛伐他汀[3,
4]、洛伐他汀[5]、普伐他汀[6]、西立伐他汀 [7]
等,深夜给药较晚上给药,药效均在分裂等级次序上更优(总胆固醇或 LDL-C
下跌幅度越来越大)。但值得注意的是,有色金属商讨所究又开采对于氟伐他汀缓释剂型 [8,
9]、辛伐他汀控制释放剂型 [10]
来说,早晚给药药效并无强烈差距。综上说述,难点的最主要在半衰期。对于短半衰期的药品,例如辛伐他汀、氟伐他汀、洛伐他汀,与早上咽下相比较,夜间咽下确实能够起到更加好的作用,那也正是以后要求他汀夜间咽下的基于了。但对缓释片和控制释放片剂型的他汀来说,早晚服用当然也就不会有差别了。为何不要求夜间咽下?可是,情随事迁,近年来的舞台大旨已经不属于他们了,而是新一代他汀:阿托伐他汀和瑞舒伐他汀的全世界。新开拓的他汀,活性更加强,作用更加持久,举个例子阿托伐他汀,半衰期长达
1四 个小时,其代谢物也有强有力的活性,使得药效半衰期进一步延伸至 20~30
h。一样,瑞舒伐他汀的半衰期也长达 二11个时辰。钻探发掘,对于阿托伐他汀和瑞舒伐他汀,早上和夜间服用时期,药效并无距离[11,
12]。有趣的是,阿托伐他汀夜间给药反而血药浓度还更低,Cmax
比午夜给药低
30%,那可能与夜间胃肠道活动弱而接受少,或是夜间代谢进程更加快有关。当然如上所述,就算Cmax
更低,总的药效却是1致的。可知,阿托伐他汀和瑞舒伐他汀并不须求夜间服用。事实上,仔细查看那二种药物表达书,上面都早就专门表达了「能够自由时间给药,且不受进食影响」。要点小结短半衰期的他汀,如辛伐他汀、氟伐他汀、洛伐他汀,确实夜间服用药效更佳。但对此缓释或控制释放剂型,以及新一代阿托伐他汀和瑞舒伐他汀,均不必要夜间服用,完全能够在早上和此外药物联合服用,防止扩展不须要的艰巨。最终,用一张表来解决种种他汀的临床及药学特点:相关数据来源自
UpToDate
临床决策数据库,感激中中原人民共和国药中国科学技术大学学陈阳硕士及其所在的实验室在药代重力学理论方面包车型客车帮扶和支撑。小编:沈亮亮排版设计:shamouer参考文献:[1].
Desai, C.S., S.S. Martin and R.S. Blumenthal, Non-cardiovascular effects
associated with statins. BMJ, 2014. 349: p. g3743.[2].
中华军事学会神经病学分会与中华工学会神经病学分会脑血管病学组,
中华人民共和国缺血性脑卒11月短暂性脑缺血发作二级防守汛抗旱指挥部南 201肆. 中华神经科杂志,

责编:

参考文献
1.Virnig BA, Tuttle TM, Shamliyan T, Kane RL. Ductal carcinoma in situ
of the breast: a systematic review of incidence, treatment, and
outcomes. J Natl Cancer Inst. 2010;102:170-8.
2.Ward EM, DeSantis CE, Lin CC, et al. Cancer statistics: breast cancer
in situ. CA Cancer J Clin. 2015;65:481-95.
3.Collins LC, Tamimi RM, Baer HJ, et al. Outcome of patients with ductal
carcinoma in situ untreated after diagnostic biopsy: results from the
Nurses Health Study. Cancer. 2005;103:1778-84.
4.Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of
low-grade ductal carcinoma in situ of the breast in women treated by
biopsy only revealed over 30 years of long-term follow-up. Cancer.
2005;103:2481-4.
5.Narod SA, Iqbal J, Giannakeas V, et al. Breast cancer mortality after
a diagnosis of ductal carcinoma in situ. JAMA Oncol. 2015;1:888-96.
6.Eusebi V, Feudale E, Foschini MP, et al. Long-term follow-up of in
situ carcinoma of the breast. Semin Diagn Pathol. 1994;11:223-35.
7.Wapnir IL, Dignam JJ, Fisher B, et al. Long-term outcomes of invasive
ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and
B-24 randomized clinical trials for DCIS. J Natl Cancer Inst.
2011;103:478-88.
8.Fisher B, Costantino J, Redmond C, et al. Lumpectomy compared with
lumpectomy and radiation therapy for the treatment of intraductal breast
cancer. N Engl J Med. 1993;328:1581-6.
9.Holmberg L, Garmo H, Granstrand B, et al. Absolute risk reductions for
local recurrence after postoperative radiotherapy after sector resection
for ductal carcinoma in situ of the breast. J Clin Oncol.
2008;26:1247-52.
10.Julien JP, Bijker N, Fentiman IS, et al. Radiotherapy in
breast-conserving treatment for ductal carcinoma in situ: first results
of the EORTC randomised phase III trial 10853. EORTC Breast Cancer
Cooperative Group and EORTC Radiotherapy Group. Lancet.
2000;355:528-33.
11.Houghton J, George WD, Cuzick J, et al. Radiotherapy and tamoxifen in
women with completely excised ductal carcinoma in situ of the breast in
the UK, Australia, and New Zealand: randomised controlled trial. Lancet.
2003;362:95-102.
12.Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of
intraductal breast cancer: National Surgical Adjuvant Breast and Bowel
Project B-24 randomised controlled trial. Lancet. 1999;353:1993-2000.
13.Early Breast Cancer Trialists’ Collaborative Group, Correa C, McGale
P, et al. Overview of the randomized trials of radiotherapy in ductal
carcinoma in situ of the breast. J Natl Cancer Inst Monogr.
2010;2010:162-77.
14.Solin LJ, Gray R, Hughes LL, et al. Surgical excision without
radiation for ductal carcinoma in situ of the breast: 12-year results
from the ECOG-ACRIN E5194 study. J Clin Oncol. 2015;33:3938-44.
15.Wong JS, Chen YH, Gadd MA, et al. Eight-year update of a prospective
study of wide excision alone for small low- or intermediate-grade ductal
carcinoma in situ (DCIS). Breast Cancer Res Treat. 2014;143:343-50.
16.McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective
randomized trial for good-risk ductal carcinoma in situ comparing
radiotherapy with observation. J Clin Oncol. 2015;33:709-15.
17.Margolese RG, Cecchini RS, Julian TB, et al. Anastrozole versus
tamoxifen in postmenopausal women with ductal carcinoma in situ
undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised,
double-blind, phase 3 clinical trial. Lancet. 2016;387:849-56.
18.Sagara Y, Freedman RA, Vaz-Luis I, et al. Patient prognostic score
and associations with survival improvement offered by radiotherapy after
breast-conserving surgery for ductal carcinoma in situ: a
population-based longitudinal cohort study. J Clin Oncol.
2016;34:1190-6.
19.Smith GL, Smith BD, Haffty BG. Rationalization and regionalization of
treatment for ductal carcinoma in situ of the breast. Int J Radiat Oncol
Biol Phys. 2006;65:1397-1403.
20.Early Breast Cancer Trialists’ Collaborative Group, Darby S, McGale
P, et al. Effect of radiotherapy after breast- conserving surgery on
10-year recurrence and 15-year breast cancer death: meta-analysis of
individual patient data for 10,801 women in 17 randomised trials.
Lancet. 2011;378:1707-16.
21.Silverstein MJ, Poller DN, Waisman JR, et al. Prognostic
classification of breast ductal carcinoma-in-situ. Lancet.
1995;345:1154-7.
22.Solin LJ, Gray R, Baehner FL, et al. A multigene expression assay to
predict local recurrence risk for ductal carcinoma in situ of the
breast. J Natl Cancer Inst. 2013;105:701-10.
23.Rakovitch E, Nofech-Mozes S, Hanna W, et al. A population-based
validation study of the DCIS Score predicting recurrence risk in
individuals treated by breast-conserving surgery alone. Breast Cancer
Res Treat. 2015;152:389-98.
24.Raldow AC, Sher D, Chen AB, et al. Cost effectiveness of the Oncotype
DX DCIS Score for guiding treatment of patients with ductal carcinoma in
situ. J Clin Oncol. 2016;34:3963-8.
25.Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of
Breast Radiotherapy (START) trials of radiotherapy hypofractionation for
treatment of early breast cancer: 10-year follow-up results of two
randomised controlled trials. Lancet Oncol. 2013;14:1086-94.
26.Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of
hypofractionated radiation therapy for breast cancer. N Engl J Med.
2010;362:513-20.
27.Ciervide R, Dhage S, Guth A, et al. Five year outcome of 145 patients
with ductal carcinoma in situ (DCIS) after accelerated breast
radiotherapy. Int J Radiat Oncol Biol Phys. 2012;83:e159-e164.
28.Lalani N, Paszat L, Sutradhar R, et al. Long-term outcomes of
hypofractionation versus conventional radiation therapy after
breast-conserving surgery for ductal carcinoma in situ of the breast.
Int J Radiat Oncol Biol Phys. 2014;90:1017-24.
29.Shah C, Vicini F, Wazer DE, et al. The American Brachytherapy Society
consensus statement for accelerated partial breast irradiation.
Brachytherapy. 2013;12:267-77.
30.Kaufman SA, Harris EE, Bailey L, et al. ACR Appropriateness Criteria®
ductal carcinoma in situ. Oncology (Williston Park). 2015;29:446-58,
460-1.
31.National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines in Oncology. Breast cancer. Version 2.2017. Updated April 6,
2017.
https://www.nccn.org/professionals/physician\_gls/pdf/breast.pdf
Accessed July 9, 2017.

10、 Rajkumar SV, Dimopoulos MA, Palumbo
A,Blade J, Merlini G, Mateos M-V, et al.:
Internationalmyelomaworking group updatedcriteria
for the diagnosis of multiple myeloma.Lancet
Oncol 15: e538–e548, 2014.

展望因素可以帮助医务卫生人士区分哪些病者更切合做放射性医治。前面所讲的Smith预测验评定分是可行的臆想工具;另2个评分工具Van
Nuys预测指数,但从没大面积利用,未有收获外界普及认同。肿瘤基因分析成为区分低、中、高危害DCIS病人的新点子。先前事关的ECOG亚组分析结果展现,低、中、高风险DCIS病者浸泡性复发率分别为4%、1二%、1九%。方今的大样本量基因分析再度评释Oncotype
DX
DCIS评分能够揣度局地复发。目前,关心点在低风险伤者的高复发率(10年复发率为13%)和性价比。预测工具或肿瘤基因检查测试能够区分哪些伤者受益于帮忙放射性医疗的数量较少。在部分病例中,这么些工具得以扶持医师和病人决定是不是利用放射疗法。

4、 Bhutani G, Nasr SH, Said SM, Sethi
S,Fervenza FC,Morice WG, et
al.:Hematologiccharacteristics of proliferative
glomerulonephritideswith nonorganized monoclonalimmunoglobulin deposits. Mayo Clin
Proc90: 587–596,2015.

四个里程碑式试验明确了放射疗法医疗DCIS的身价。四个随机试验相比了胸部肿瘤切除后帮助放射性医治和无放射性医治的效力,分别是美利坚独资国国度眼科辅助诊治乳腺和肠道项目(NSABP)B-一七试验、SweDIC试验、亚洲癌症研商和治疗团队10捌伍三试验、大不列颠及北爱尔兰联合王国癌症研商协作组织试验。种种试验都认证加用放射疗法能减小1/2的同侧浸泡性乳头内陷复发率(IBT福特Explorer)。全部多个研商都声明了加用放射性诊治能强烈收缩浸泡性复发、减弱外阴痛死亡率。不过这几个试验或对那一个试验的云集分析结果不能够证实放射疗法能拉开伤者总生存时间。

The Complexity and Heterogeneity of
Monoclonal Immunoglobulin-Associated Renal Diseases. J Am Soc Nephrol.
2018 Jul;29(7):1810-1823.

些微人觉着,由于并未人身自由临床试验能注脚支持放射性医疗能延长病人总生存时间,那么大多DCIS病者乳房肿瘤切除后不用接受放射性医治。在随同访问进程中精心监测病情,如有指征时放射性治疗可看做挽救性治疗。不过放疗不可能延长伤者生活时间不等于没意义。拾年的DCIS相关阴道炎特定去世率唯有3%。

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DCIS医疗去放射性医疗的尝试

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