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The unexpected costs of “free” preventive care “免费”预防性护理的意外成本
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-11-01 DOI: 10.1002/cncy.22775
Bryn Nelson PhD, William Faquin MD, PhD

Stool-based colorectal cancer tests, boosted by their noninvasive nature and the federal requirement that they be covered at no cost to insured patients as a free preventive screen, have surged in popularity. Until recently, however, a positive test result could prompt a surprise bill for a follow-up colonoscopy—one of many examples of how the promise of widely accessible cancer screening still faces substantial hurdles.

In 2010, the Affordable Care Act heralded a major shift in how preventive care is handled in the United States. Among its many provisions, the act requires private insurers to fully cover, at no cost to consumers, preventive services endorsed by one of three groups: the Advisory Committee on Immunization Practices, the Health Resources and Services Administration, or the US Preventive Services Task Force (USPSTF).

To date, the law has made screening for colorectal, cervical, breast, and lung cancers—all of which have received an A or B rating from the USPSTF—freely available for eligible individuals. In practice, health policy experts such as Mark Fendrick, MD, director of the University of Michigan’s Center for Value-Based Insurance Design in Ann Arbor, have noted that “free” is not always free for what is more often a screening continuum than a single test. In one case, he learned about a patient who had to pay more than $1000 for a follow-up colonoscopy after a positive stool-based DNA test. “I blew a gasket,” says Dr Fendrick, who helped to write the Affordable Care Act’s preventive services provision.

If a gastroenterologist removed a polyp during a colonoscopy, some medical institutions also changed the billing code from a preventive screen to a therapeutic intervention; this switch was dubbed the “post polypectomy surprise.” Such recoding defeats the whole point of preventive care, says Paul Shafer, PhD, an assistant professor of health law, policy, and management at the Boston University School of Public Health in Massachusetts. “If they cut polyps out, great—that’s a good thing,” he says. “I don’t think that we should be penalizing the patient for doing the thing that we’ve tried to incentivize them to do through this policy.”

To better understand the magnitude of the problem, Dr Fendrick and his collaborators assessed how often and how much patients paid after receiving a positive test result for each of the four cancers in the USPSTF screening recommendations and how those costs were changing over time. For all four, they documented some surprisingly common charges.

In a 2021 JAMA Network Open study of 88,000 patients, Dr Fendrick and his colleagues found that among the more than 1 in 6 who had a stool-based test and underwent a follow-up colonoscopy within 6 months, nearly half with commercial insurance incurred out-of-pocket costs.1 For Medicare patients, more than three quarters had to pay out of pocket. A similar study found that after an initial mammo

以粪便为基础的癌症大肠癌检测,由于其非侵入性和联邦要求作为免费预防性筛查免费为投保患者提供服务的要求,受到了推动,其受欢迎程度激增。然而,直到最近,阳性检测结果可能会引发一项令人惊讶的后续结肠镜检查法案——这是广泛接受癌症筛查的前景仍然面临巨大障碍的众多例子之一。2010年,《平价医疗法案》预示着美国处理预防性医疗的方式发生了重大转变。在其众多条款中,该法案要求私人保险公司免费为三个团体之一认可的预防服务提供全额保险:免疫实践咨询委员会、卫生资源和服务管理局或美国预防服务工作队(USPSTF),和肺癌——所有这些都获得了USPSTF的A级或B级——对符合条件的个人免费提供。在实践中,密歇根大学安娜堡基于价值的保险设计中心主任、医学博士Mark Fendrick等健康政策专家指出,“免费”并不总是免费的,因为筛查往往是连续的,而不是单一的测试。在一个案例中,他了解到一名患者在粪便DNA检测呈阳性后,不得不支付1000多美元进行后续结肠镜检查。芬德里克博士说:“我搞砸了一个垫圈。”他帮助起草了《平价医疗法案》的预防服务条款。如果胃肠科医生在结肠镜检查中切除了息肉,一些医疗机构也将账单代码从预防性筛查改为治疗性干预;这种转变被称为“息肉切除术后的惊喜”。马萨诸塞州波士顿大学公共卫生学院卫生法律、政策和管理助理教授Paul Shafer博士说,这种记录破坏了预防性护理的全部意义。“如果他们能切除息肉,那就太好了——这是一件好事,”他说。“我不认为我们应该因为患者做了我们试图通过这项政策激励他们做的事情而惩罚他们。”为了更好地理解问题的严重性,Fendrick博士和他的合作者评估了患者在收到USPSTF筛查建议中四种癌症中每种癌症的阳性检测结果后支付的频率和金额,以及这些费用是如何随着时间的推移而变化的。对于这四人,他们记录了一些令人惊讶的常见指控。在2021年《美国医学会杂志》网络公开版对88000名患者进行的一项研究中,芬德里克博士和他的同事发现,在超过六分之一的患者进行了粪便检测并在6个月内接受了后续结肠镜检查,其中近一半的患者购买了商业保险,费用自付。1对于医疗保险患者,超过四分之三的患者必须自付。一项类似的研究发现,在最初的乳房X光检查后,年龄在40岁至64岁之间的商业保险女性通常会因额外的乳房成像评估和手术而产生“不寻常”的自费费用,而且这些费用随着时间的推移而增加。2芬德里克博士说,在癌症筛查中检测呈阳性是一个“可怕、可怕的时期”。“你不仅担心自己可能患上癌症,而且还不得不根据你是谁和你有什么保险而自掏腰包。”美国各地预防服务实施方式的巨大差异导致了其他意外成本。Shafer博士和波士顿大学的一位同事在2021年进行的一项研究估计,每年向患者收取7560万至2.19亿美元的预防性护理费用,这些费用本应由他们的健康保险公司免费承保,但事实并非如此。3 Shafer博士指出,这项研究纯粹着眼于本应免费的服务,而不是任何后续测试。他说:“如果你真的考虑到后续行动的成本,我们的估计会高得多。”。Shafer博士说,关键问题是《平价医疗法案》规定了哪些服务必须免费覆盖,但每个保险公司和每个保险计划随后决定如何将这一要求付诸实践,以及使用哪些诊断代码和当前程序术语(CPT)代码。他说:“在许多不同的商业健康计划下,有很多不同的患者,他们对如何向患者免费收费的指导方针都略有不同。”。“毫不奇怪,有时事情会漏洞百出。”通常情况下,患者会试图制定账单指南以及应该涵盖哪些预防服务。Shafer博士说:“大多数人都做不到——这太复杂了,所以他们感到沮丧。”。
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引用次数: 0
Erratum to “p53 expression in cytology samples may represent a marker of early-stage cancer” “细胞学样本中p53表达可能代表早期癌症的标志物”的勘误表。
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-21 DOI: 10.1002/cncy.22773

This erratum corrects the following:

Policardo F, Tralongo P, Arciuolo D, et al. p53 expression in cytology samples may represent a marker of early-stage cancer. Cancer Cytopathol. 2023;131(6):392-401. doi:10.1002/cncy.22694

Please note that the surname of one of the authors, Lina Cardisciani, was misspelled as “Cardasciani.”

The authors regret this error.

本勘误更正如下:Policardo F, Tralongo P, Arciuolo D, et al. 细胞学样本中 p53 的表达可能是早期癌症的标志物。Cancer Cytopathol.2023;131(6):392-401.doi:10.1002/cncy.22694请注意,作者之一 Lina Cardisciani 的姓氏拼错为 "Cardasciani"。
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引用次数: 0
Thank You to Reviewers 2023 感谢审稿人 2023
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-18 DOI: 10.1002/cncy.22774

Cancer Cytopathology’s reputation is determined by the quality of the manuscripts submitted and the expertise, dedication, and promptness of the individuals who critically review the manuscripts. In this issue, we’d like to congratulate and acknowledge our top reviewers for their outstanding peer review efforts from the period spanning from September 1, 2022, through August 31, 2023. These individuals go beyond expectations by consistently and expeditiously delivering comprehensive, discerning reviews. The criteria involved in these selections include the number of reviews conducted per year, and the timeliness of review completion. Cancer Cytopathology wishes to thank and congratulate the following conscientious and committed reviewers who are the 2023 recipients of this recognition.

Longwen Chen

Monique Courtade-Saidi

Diane Davey

Tadao Kobayashi

Daniel Kurtycz

Oscar Lin

Panagiota Mikou

Sara Monaco

David Poller

Mauro Saieg

Momin Siddiqui

Vanda Torous

Giancarlo Troncone

Christopher VandenBussche

Vivian Weiss

Mingjuan Zhang

We also wish to express our sincere appreciation to all other individuals who reviewed manuscripts for the journal in this time period.

Adebowale Adeniran

Derek Allison

Trevor Angell

Tatjana Antic

Manon Auger

Ronald Balassanian

Tejus Bale

Guliz Barkan

Claudio Bellevicine

Brendan Belovarac

Cory Bernadt

George Birdsong

Christine Booth

Tamar Brandler

Lukas Bubendorf

Guoping Cai

Ashish Chandra

Ivan Chebib

Athena Chen

Chien-Chin Chen

Lan Chen

Megan Clarke

Rubina Cocker

Immacolata Cozzolino

William Crabtree

Barbara Crothers

Suzanne Crumley

Gilda da Cunha Santos

Luis De Las Casas

Qingqing Ding

Leslie Dodd

Erika Doxtader

Catarina Eloy

Kim Ely

Guido Fadda

Andrew Field

Armando Filie

Mary Frates

Franco Fulciniti

Qiong Gan

Hamza Gokozan

Abha Goyal

Rosario Granados

Christopher Griffith

Ming Guo

Jen-Fan Hang

Jonas Heymann

Brittany Holmes

Jason Hornick

Eric Huang

Peter Illei

Deepali Jain

Xiaoyin "Sara" Jiang

Fengyi Jin

Xin Jing

Chan Kwon Jung

Darcy Kerr

Ivana Kholová

Kamal Khurana

Jerzy Klijanienko

Richard Kloos

Omar Kujan

Madelyn Lew

Zaibo Li

Xiaoqi Lin

Zixing Liu

Steven Long

Adhemar Longatto-Filho

Alarice Lowe

Maria D. Lozano

Amy Ly

Umberto Malapelle

Zahra Maleki

Varsha Manucha

Meenakshi Mehrotra

Claire Michael

Daniel Miller

Jeffrey Mito

Andre Moreira

Sanjay Mukhopadhyay

Aziza Nassar

Ritu Nayar

N Paul Ohori

Liron Pantanowitz

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癌症细胞病理学》的声誉取决于所投稿件的质量以及审稿人的专业知识、敬业精神和审稿速度。在本期杂志中,我们要祝贺并感谢我们的顶级审稿人在 2022 年 9 月 1 日至 2023 年 8 月 31 日期间所做的杰出同行评审工作。这些人始终如一地迅速提供全面、独到的审稿意见,超越了人们的期望。评选标准包括每年的审稿数量和审稿完成的及时性。癌症细胞病理学》感谢并祝贺以下认真负责的审稿人成为 2023 年度的获奖者。Longwen ChenMonique Courtade-SaidiDiane DaveyTadao KobayashiDaniel KurtyczOscar LinPanagiota MikouSara MonacoDavid PollerMauro SaiegMomin SiddiquiVanda TorousGiancarlo TronconeChristopher VandenBusscheVivian Weiss张明娟我们还要向在此期间为本刊审稿的所有其他人员表示衷心的感谢。Adebowale AdeniranDerek AllisonTrevor AngellTatjana AnticManon AugerRonald BalassanianTejus BaleGuliz BarkanClaudio BellevicineBrendan BelovaracCory BernadtGeorge BirdsongChristine BoothTamar BrandlerLukas BubendorfGuoping CaiAshish ChandraIvan ChebibAthena Chen陈千帆陈建兰Megan ClarkeRubina CockerImmacolata CozzolinoWilliam CrabtreeBarbara CrothersSuzanne CrumleyGilda da Cunha SantosLuis De Las Casas丁青青Leslie DoddErika多克斯达德卡塔琳娜-埃罗伊金-伊利吉多-法达安德鲁-菲尔德阿曼多-菲利玛丽-弗拉茨弗兰科-富尔奇尼蒂琼-甘哈姆扎-戈科赞阿巴-戈亚尔罗萨里奥-格拉纳多斯克里斯托弗-格里菲斯郭明简-范-杭约纳斯-海曼B.杭帆Jonas HeymannBrittany HolmesJason HornickEric HuangPeter IlleiDeepali Jain蒋小银 "Sara "Jiang金凤仪金鑫景陈权JungDarcy KerrIvana KholováKamal KhuranaJerzy KlijanienkoRichard KloosOmar KujanMadelyn Lew李在波林晓琪刘子兴Steven LongAdhemar Longatto-FilhoAlarice LoweMaria D. LozanoAmy LymberUmberLozanoAmy LyUmberto MalapelleZahra MalekiVarsha ManuchaMeenakshi MehrotraClaire MichaelDaniel MillerJeffrey MitoAndre MoreiraSanjay MukhopadhyayAziza NassarRitu NayarN Paul OhoriLiron PantanowitzMartha PitmanMaria Luisa Policarpio-尼古拉斯-伊-波因滕马克-普什塔斯泽里钱晓华饶瑞玛安德鲁-伦肖乔丹-雷诺兹迈克尔-里本劳伦-里特豪斯丽莎-罗珀罗伯托-鲁伊斯-科德罗巴里-萨克CorderoBarry SacksPeter SadowJennifer SauterFernando SchmittMary SchwartzMatheus Sewastjanow-SilvaAatur SinghiPaul StaatsEdward StelowKaitlin SundlingMichael ThrallPierpaolo TrimboliGary TseLouis VaickusPaul VanderLaanJaylou Velez-TorresElena VigliarKartik ViswanathanMarina ViveroPoonam VohraHe WangNicolas WentzensenBirgit WeynandBenjamin WittEva WojcikHoward WuJack YangKeluo YaoMaureen ZakowskiPio ZeppaChengquan ZhaoHaijun ZhouRosemary Zuna
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引用次数: 0
Bridging the gap to the next generation of learners and column leadership 弥补与下一代学习者和专栏领导之间的差距。
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-17 DOI: 10.1002/cncy.22771
Diane Davis Davey MD, Sara E. Monaco MD
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引用次数: 0
Molecular-derived risk of malignancy and the related positive call rate of indeterminate thyroid cytology diagnoses as quality metrics for individual cytopathologists 分子衍生的恶性肿瘤风险和不确定的甲状腺细胞学诊断的相关阳性率作为个体细胞病理学家的质量指标。
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-17 DOI: 10.1002/cncy.22772
N. Paul Ohori MD, Jacqueline M. Cuda BS, SCT, Sheldon I. Bastacky MD, Linwah Yip MD, Esra Karslioglu-French MD, Elena M. Morariu MD, Jagdeesh Ullal MD, Kimberly M. Ramonell MD, Sally E. Carty MD, Yuri E. Nikiforov MD, PhD, Karen E. Schoedel MD, Raja R. Seethala MD

Background

Indeterminate thyroid cytopathology diagnoses represent differing degrees of risk that are corroborated by follow-up studies. However, traditional cytologic–histologic correlation may overestimate the risk of malignancy (ROM) because only a subset of cases undergo resection. Alternatively, some molecular tests provide probability of malignancy data to calculate the molecular-derived risk of malignancy (MDROM) and the positive call rate (PCR). The authors investigated MDROMs and PCRs of indeterminate diagnoses for individual cytopathologists as quality metrics.

Methods

This study was approved by the Department of Pathology Quality Improvement Program. Thyroid cytopathology diagnoses and ThyroSeq v3 results were retrieved for each cytopathologist for a 2-year period with at least 3 years of follow-up for the atypia of undetermined significance (AUS), follicular neoplasia (FN), and follicular neoplasia, oncocytic-type (ONC) cytopathologic diagnoses. MDROMs and PCRs were compared with reference ROMs and cytologic–histologic correlation outcomes.

Results

The overall MDROMs (and ranges for cytopathologists) for the AUS, FN, and ONC categories were 13.4% (range, 5.8%–20.8%), 28.1% (range, 22.1%–36.7%), and 27.0% (range, 19.5%–41.5%), respectively, and most individual cytopathologists' MDROMs were within reference ROM ranges. However, PCRs more effectively parsed the differences in cytopathologists' ROM performance. Although the overall PCRs were not significantly different across cytopathologists (p = .06), the AUS PCRs were quite different (p = .002). By cytologic–histologic correlation, six of 55 resected cases (10.9%) were falsely negative, and there were no false-positive cases.

Conclusions

MDROMs and PCRs evaluate concordance with reference ROMs and with one another and provide individual feedback, which potentially facilitates quality improvement.

背景:未确定的甲状腺细胞病理学诊断代表了不同程度的风险,后续研究证实了这一点。然而,传统的细胞学组织学相关性可能高估了恶性肿瘤(ROM)的风险,因为只有一小部分病例进行了切除。或者,一些分子测试提供恶性肿瘤的概率数据,以计算分子衍生的恶性肿瘤风险(MDROM)和阳性呼叫率(PCR)。作者调查了个体细胞病理学家不确定诊断的MDROM和PCRs作为质量指标。方法:本研究经病理科质量改进计划批准。检索每位细胞病理学家的甲状腺细胞病理学诊断和ThyroSeq v3结果,为期2年,对意义不明的异型性(AUS)、滤泡性肿瘤(FN)和滤泡性肿瘤、嗜酸细胞型(ONC)细胞病理学的诊断进行至少3年的随访。MDROM和PCRs与参考ROM和细胞学组织学相关性结果进行比较。结果:AUS、FN和ONC类别的总MDROM(以及细胞病理学家的范围)分别为13.4%(范围5.8%-20.8%)、28.1%(范围22.1%-36.7%)和27.0%(范围19.5%-41.5%),大多数细胞病理学家都在参考ROM范围内。然而,聚合酶链式反应更有效地解析了细胞病理学家ROM表现的差异。尽管细胞病理学家的总体PCRs没有显著差异(p=0.06),但AUS PCRs却有很大差异(p=0.002)。根据细胞学组织学相关性,55例切除病例中有6例(10.9%)为假阴性,没有假阳性病例。结论:MDROM和PCRs评估与参考ROM以及彼此之间的一致性,并提供个人反馈,这可能有助于质量改进。
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引用次数: 0
Unlocking the potential of organoids in cancer treatment and translational research: An application of cytologic techniques 释放类器官在癌症治疗和转化研究中的潜力:细胞学技术的应用。
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-16 DOI: 10.1002/cncy.22769
Mohamed A. Abd El-Salam PharmD, MS, PhD, Maria J. Troulis DDS, MS, Chong-Xian Pan MD, PhD, MAS, Rema A. Rao MD

Patient-derived organoid models hold promise for advancing clinical cancer research, including diagnosis and personalized and precision medicine approaches, and cytology, in particular, plays a pivotal role in this process. These three-dimensional multicellular structures are heterogeneous, potentially maintain the cancer phenotype, and conserve the genomic, transcriptomic, and epigenomic patterns of the parental tumors. To ensure that only tumor tissue is used for organoid development, cytologic validation is necessary before initiating the process of organoid generation. Here, we explore the technology of tumor organoids and discuss the fundamental application of cytology as a simple and cost-effective approach toward organoid development. We also underscore the potential application of organoid development in drug efficacy studies for lung cancer and head and neck tumors. Additionally, we stress the importance of using fine-needle aspiration to generate tumoroids.

患者来源的类器官模型有望推进癌症临床研究,包括诊断、个性化和精准医疗方法,尤其是细胞学在这一过程中发挥着关键作用。这些三维多细胞结构是异质性的,可能维持癌症表型,并保存亲代肿瘤的基因组、转录组和表观基因组模式。为了确保只有肿瘤组织用于类器官发育,在启动类器官生成过程之前,需要进行细胞学验证。在这里,我们探索了肿瘤类器官的技术,并讨论了细胞学作为一种简单且具有成本效益的类器官开发方法的基本应用。我们还强调了类器官开发在癌症和头颈部肿瘤药物疗效研究中的潜在应用。此外,我们强调了使用细针抽吸产生类肿瘤的重要性。
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引用次数: 0
Fine-needle aspiration biopsy of axillary lymph nodes: A reliable diagnostic tool for breast cancer staging 腋窝淋巴结细针穿刺活检:乳腺癌症分期的可靠诊断工具。
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-16 DOI: 10.1002/cncy.22770
Luai Sallout MD, Mohamed Tashkandi MD, Amani Moqnas CT(IAC), Hebah AlMajed CT(IAC), Abdulrhman Al-Naeem MD, Yazeed Alwelaie MD, FRCPC

Background

Pathologic evaluation of sentinel lymph node biopsy (SLNB) samples is crucial for axillary staging in patients newly diagnosed with breast cancer. Patients with pathologic evidence of nodal metastasis scheduled for upfront surgery typically also undergo axillary lymph node dissection (ALND). Although SLNB is the gold standard method for detecting nodal metastasis, axillary lymph node fine-needle aspiration biopsy (FNAB) utility has not been thoroughly explored.

Methods

Ultrasound-guided axillary lymph node FNAB samples along with concurrent ipsilateral breast tissue samples were searched and reviewed. The control group included histologic findings of axillary dissection or intraoperative SLNB results.

Results

A total of 354 axillary lymph node FNAB samples with matched histology were included. Of these, 187 (52.8%) were positive for metastatic carcinoma of breast origin; 143 (40.4%) were negative for metastasis; 12 (3.4%) showed atypical cells; six (1.7%) were suspicious for metastasis; and six (1.7%) were nondiagnostic because of a lack of lymphoid tissue and malignant cells. Of the 143 negative FNAB samples, 22 (15.4%) were positive on either intraoperative SLNB or ALND. When only the positive and negative FNAB samples were accounted for (n = 330; 93.2%), overall diagnostic sensitivity and specificity were 89.4% and 99.2%, respectively.

Conclusions

Although axillary SLNB is the standard procedure for detecting nodal metastasis of breast origin, axillary lymph node FNAB appears to be a suitable alternative in a significant proportion of patients. A standard SLNB should be performed in cases of negative axillary lymph node FNAB findings, particularly nodes with abnormal imaging findings.

背景:前哨淋巴结活检(SLNB)样本的病理学评估对于新诊断的癌症患者的腋窝分期至关重要。有淋巴结转移病理证据的患者计划进行前期手术,通常也要进行腋窝淋巴结清扫(ALND)。尽管SLNB是检测淋巴结转移的金标准方法,但腋窝淋巴结细针抽吸活检(FNAB)的实用性尚未得到彻底探索。方法:对超声引导下腋窝淋巴结FNAB样本以及同期同侧乳腺组织样本进行检索和回顾。对照组包括腋窝解剖的组织学表现或术中SLNB结果。结果:共纳入354份组织学匹配的腋窝淋巴结FNAB样本。其中187例(52.8%)为乳腺转移癌阳性;转移阴性143例(40.4%);非典型细胞12例(3.4%);6例(1.7%)可疑转移;6例(1.7%)因缺乏淋巴组织和恶性细胞而未被诊断。在143个阴性FNAB样本中,22个(15.4%)在术中SLNB或ALND中呈阳性。当仅考虑阳性和阴性FNAB样本时(n=330;93.2%),总体诊断敏感性和特异性分别为89.4%和99.2%。结论:尽管腋窝SLNB是检测乳腺源性淋巴结转移的标准方法,但在相当大比例的患者中,腋窝淋巴结FNAB似乎是一种合适的替代方法。如果腋窝淋巴结FNAB检查结果为阴性,特别是影像学检查结果异常的淋巴结,应进行标准的SLNB检查。
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引用次数: 0
Urinary IL-6 and IL-8 as predictive markers in bladder urothelial carcinoma: A pilot study 尿IL-6和IL-8作为膀胱尿路上皮癌的预测标志物:一项初步研究。
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-09 DOI: 10.1002/cncy.22767
Christopher J. VandenBussche MD, PhD, Christopher D. Heaney PhD, MS, Max Kates MD, John J. Hooks PhD, Kelly Baloga MLS(ASCP)CM, Lori Sokoll PhD, Dorothy Rosenthal MD, Barbara Detrick PhD

Background

Cytokines are known to be a key a factor in numerous malignancies and to exert an important regulatory role in the tumor microenvironment. Interest has grown in understanding how cytokines modulate the tumor microenvironment and which cytokines may serve as markers of the tumor process; however, a complete picture of the cytokine landscape in bladder cancer remains unclear.

Methods

Fresh urine specimens with sufficient volume were collected at random intervals. The urine concentrations of IL-8 (CXCL8), CCL18, and CXCL9 were determined using the standard commercially available enzyme immunoassay. The urine concentrations of IL-6 were determined using the high sensitivity enzyme immunoassay kit. Urinary cytokine concentrations were normalized with urinary creatinine concentrations.

Results

Significantly elevated concentrations of IL-6 and IL-8 were detected in the urine from patients with urothelial carcinoma on follow-up compared to patients with benign follow-up. The presence of both IL-6 and IL-8 in the urine samples from the high grade urothelial carcinoma (HGUC) cohort revealed a clear discrimination when compared to samples from patients with benign follow-up. The presence of the combination of both IL-6 and IL-8 had a sensitivity of 90.0% and a specificity of 81.25%. Similar data were obtained when receiver operating characteristic analysis was performed on both IL-6 and IL-8 concentrations in the urine from patients with HGUC vs. the hematuria cohort.

Conclusions

The presence of IL-6 and IL-8 in urine specimens may have predictive value for urothelial carcinoma. However, a large longitudinal study is required to statistically eliminate confounding factors and support this theory.

背景:众所周知,细胞因子是许多恶性肿瘤的关键因子,并在肿瘤微环境中发挥重要的调节作用。人们对了解细胞因子如何调节肿瘤微环境以及哪些细胞因子可以作为肿瘤过程的标志物越来越感兴趣;然而,细胞因子在膀胱癌症中的完整情况仍不清楚。方法:随机采集足够容量的新鲜尿液标本。使用标准市售酶免疫测定法测定IL-8(CXCL8)、CCL18和CXCL9的尿液浓度。使用高灵敏度酶免疫测定试剂盒测定尿液中IL-6的浓度。尿细胞因子浓度用尿肌酐浓度标准化。结果:与良性随访患者相比,随访中尿路上皮癌患者尿液中IL-6和IL-8浓度显著升高。与良性随访患者的尿液样本相比,来自高级别尿路上皮癌(HGUC)队列的尿液样本中IL-6和IL-8的存在显示出明显的区别。IL-6和IL-8联合存在的敏感性为90.0%,特异性为81.25%。当对HGUC患者与血尿队列的尿液中IL-6和IL-8%浓度进行受试者操作特征分析时,获得了类似的数据。结论:尿液中IL-6和IL-8的存在可能对尿路上皮癌具有预测价值。然而,需要进行大规模的纵向研究,以从统计上消除混杂因素并支持这一理论。
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引用次数: 0
Validation of targeted next-generation sequencing of cell-free DNA from archival cerebrospinal fluid specimens for the detection of somatic variants in cancer involving the leptomeninges: Cytopathologic and radiographic correlation 从档案脑脊液样本中靶向下一代无细胞DNA测序用于检测涉及软脑膜的癌症体细胞变异的验证:细胞病理学和放射学相关性。
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-09 DOI: 10.1002/cncy.22768
Alexander J. Neil MD, PhD, Ugonma N. Chukwueke MD, MPH, Nicholas Hoover CT (ASCP), Sean R. N. Marris BS, Vanesa Rojas-Rudilla MS, Danielle K. Manning PhD, Jeffrey K. Mito MD, PhD, Edmund S. Cibas MD, Lynette M. Sholl MD

Background

Leptomeningeal metastases occur across multiple solid and lymphoid cancers, and patients typically undergo cytopathologic assessment of cerebrospinal fluid (CSF) in this setting. For patients diagnosed with metastatic cancer, the detection of actionable somatic mutations in CSF can provide clinically valuable information for treatment without the need for additional tissue collection.

Methods

The authors validated a targeted next-generation sequencing assay for the detection of somatic variants in cancer (OncoPanel) on cell-free DNA (cfDNA) isolated from archival CSF specimens in a cohort of 25 patients who had undergone molecular testing of a prior tumor specimen.

Results

CSF storage time and volume had no impact on cfDNA concentration or mean target coverage of the assay. Previously identified somatic variants in CSF cfDNA were detected in 88%, 50%, and 27% of specimens diagnosed cytologically as positive, suspicious/atypical, and negative for malignancy, respectively. Somatic variants were identified in 81% of CSF specimens from patients who had leptomeningeal enhancement on magnetic resonance imaging compared with 31% from patients without such enhancement.

Conclusions

These data highlight the stability of cfDNA in CSF, which allows for cytopathologic evaluation before triage for next-generation sequencing assays. For a subset of cases in which clinical suspicion is high but cytologic or radiographic studies are inconclusive, the detection of pathogenic somatic variants in CSF cfDNA may aid in the diagnosis of leptomeningeal metastases.

背景:瘦素转移发生在多种实体癌和淋巴癌中,在这种情况下,患者通常会接受脑脊液(CSF)的细胞病理学评估。对于被诊断为转移性癌症的患者,检测CSF中可操作的体细胞突变可以为治疗提供有临床价值的信息,而不需要额外的组织收集。方法:作者验证了一种用于检测癌症体细胞变异的靶向下一代测序方法(OncoPanel),该方法从25名患者的档案CSF样本中分离出无细胞DNA(cfDNA),这些患者对先前的肿瘤样本进行了分子检测。结果:CSF储存时间和体积对cfDNA浓度或检测的平均靶点覆盖率没有影响。在细胞学诊断为恶性肿瘤阳性、可疑/非典型和阴性的标本中,分别有88%、50%和27%检测到先前在CSF cfDNA中发现的体细胞变体。在磁共振成像上有软脑膜增强的患者的81%的CSF样本中发现了体细胞变异,而在没有增强的患者中这一比例为31%。结论:这些数据突出了cfDNA在CSF中的稳定性,这使得在下一代测序分析分型之前可以进行细胞病理学评估。对于临床怀疑度高但细胞学或放射学研究不确定的病例子集,在CSF cfDNA中检测致病性体细胞变异可能有助于诊断软脑膜转移。
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引用次数: 0
Understanding the “zombie cells” that won’t die 了解不会死亡的“僵尸细胞”
IF 3.4 3区 医学 Q2 Medicine Pub Date : 2023-10-03 DOI: 10.1002/cncy.22765
Bryn Nelson PhD, William Faquin MD, PhD

Here is a line you do not hear every day in cancer research: How can we control that zombie?

In response to various forms of stress after birth, such as cancer, human cells can shift into a defensive crouch called senescence, which is marked by sharply reduced activity. In this altered state, the cells stop dividing, grow in size, become somewhat disorganized, and start pumping out an array of functionally diverse factors. Much like zombies, they also refuse to die easily.

As researchers are finding, these dynamic but poorly understood “zombie cells,” as they have been dubbed, are full of contradictions. In one form, they can hold some cancers at bay for years. A premalignant colorectal polyp, for example, can be composed of a clump of senescent cells that remain relatively stable over time. Certain oncogenes, however, can thwart the defense by reanimating the cells and forcing them to resume their uncontrolled replication.

As an alternative to another cancer defense known as programmed cell death, or apoptosis, senescence is far less predictable. “Apoptosis is more like live or die; it’s binary, right? But senescence is nothing like it,” says Masashi Narita, MD, PhD, a professor of senobiology at the University of Cambridge in the United Kingdom. “It’s a progressive and a heterogeneous phenotype, so it’s very difficult to say [whether] senescence is a good thing or a bad thing.”

Depending on the context, it may be both. In April 2023, at the annual meeting of the American Association for Cancer Research, Dr Narita and other experts spoke at a special session about senescent cells’ “double-edged sword.” Senescent cells induced by oncogenes such as MYC do not die easily, Dr Narita notes, in part because they are resistant to apoptosis. That transition, in other words, undermines another means of cellular defense. The early stages of the slowdown can also increase plasticity in a way that promotes cancer development through other mechanisms.

Some cancer interventions yield therapy-induced senescence, only to be undone by a mechanism called senescence-associated secretory phenotype (SASP). As part of SASP, cells release a stew of factors, including proinflammatory proteins that can promote tumorigenesis. Conversely, interventions such as chimeric antigen receptor T-cell therapy hinge on cancer’s hallmark of rapidly dividing cells; this means that senescence can limit the therapy’s effectiveness.

Despite the many complexities, or perhaps because of them, the field of cancer-associated senescence is booming. Ricardo Iván Martínez Zamudio, PhD, an assistant professor of pharmacology at Robert Wood Johnson Medical School and a research member of the Rutgers Cancer Institute of New Jersey in New Brunswick, recalls that the phenomenon was once labeled a cell culture artifact with no medical relevance. “But it’s just exploding! There are now more and more people interested in senescence,” he says.

A quarter-cent

在癌症研究中,你每天都听不到这样一句话:我们如何控制僵尸?为了应对出生后的各种形式的压力,如癌症,人类细胞可以转变为一种称为衰老的防御状态,其特征是活动急剧减少。在这种改变的状态下,细胞停止分裂,体积增大,变得有些无序,并开始分泌一系列功能多样的因子。就像僵尸一样,他们也拒绝轻易死去。正如研究人员所发现的那样,这些动态但鲜为人知的“僵尸细胞”充满了矛盾。在一种形式中,它们可以抑制一些癌症数年。例如,癌前结肠息肉可以由一团随着时间的推移保持相对稳定的衰老细胞组成。然而,某些致癌基因可以通过使细胞复活并迫使它们恢复不受控制的复制来阻止防御。作为另一种被称为程序性细胞死亡或凋亡的癌症防御的替代方案,衰老远不可预测。英国剑桥大学senobiology教授、医学博士Masashi Narita说:“细胞凋亡更像是生或死;它是二元的,对吧?但衰老一点也不像。”。“这是一种进行性和异质性表型,所以很难说衰老是好事还是坏事。”根据具体情况,两者都可能。2023年4月,在美国癌症研究协会年会上,成田博士和其他专家在一次特别会议上谈到了衰老细胞的“双刃剑”。成田博士指出,由MYC等致癌基因诱导的衰老细胞不容易死亡,部分原因是它们对细胞凋亡具有抵抗力。换句话说,这种转变破坏了另一种细胞防御手段。减缓的早期阶段也可以增加可塑性,通过其他机制促进癌症的发展。一些癌症干预产生了治疗诱导的衰老,但被称为衰老相关分泌表型(SASP)的机制所破坏。作为SASP的一部分,细胞会释放一系列因子,包括可以促进肿瘤发生的促炎蛋白。相反,嵌合抗原受体T细胞治疗等干预措施取决于癌症细胞快速分裂的标志;这意味着衰老会限制治疗的有效性。尽管存在许多复杂性,或者可能正是因为这些复杂性,癌症相关衰老领域正在蓬勃发展。罗伯特·伍德·约翰逊医学院药理学助理教授、新不伦瑞克新泽西州罗格斯癌症研究所研究成员Ricardo Iván Martínez Zamudio博士回忆说,这种现象曾被标记为与医学无关的细胞培养产物。“但它正在爆炸!现在有越来越多的人对衰老感兴趣,”他说。四分之一个世纪前,研究人员发现,某些致癌基因引起的癌细胞异常快速复制会引发衰老减缓。然而,在这种看似平静的时期,这些细胞可以表现出一系列动态的行为:一些细胞鼓励免疫细胞自行清除,而另一些细胞似乎阻止了这种降解,并促进了癌症和其他与年龄相关的疾病。Martínez Zamudio博士认为,过渡状态及其SASP机制可能会让压力细胞有机会评估周围环境,并在可能的情况下,恢复到半正常状态或至少更稳定的状态。然而,作为寻求正常状态的潜在副作用,一些SASP因子可以促进有丝分裂,从而推动癌症细胞增殖的恢复。在最近的一项研究中,Martínez Zamudio博士展示了低活性衰老细胞如何在结直肠癌癌症中复活,从而为恶性肿瘤利用防御系统的一种方式提供了新的线索,他和他的同事们发现,细胞衰老会引发一系列相关转录因子的调控缺失,而这些转录因子原本可以控制哪些基因的开启和关闭。“我们发现,我们模型系统中的AP1转录因子家族似乎对介导衰老的进入和退出至关重要,”他说。AP1转录因子与另一种名为POU2F2的转录因子结合,通过重新激活细胞周期、重新编程和炎症促进基因,将衰老细胞从睡眠中赶走。在癌症细胞中,研究人员看到了同样的过程。更直接地说,如果进一步的研究继续表明POU2F2与结直肠癌癌症细胞衰老的逃避有关,这可能会促使人们寻找与该蛋白结合并使其失效的药物,从而阻止细胞增殖的恢复。 他说:“随着在一个更相关的系统和一些组织样本中进行更多的验证,我认为POU2F2可能成为一个靶点。”至少对于致癌基因相关癌症的一个子集来说是这样。然而,Martínez Zamudio博士警告说,SASP的复杂性可能会限制研究结果的更广泛适用性。他说:“这是一件非常复杂的事情。衰老细胞的状态实际上取决于最初的触发因素和细胞类型。”。“我不认为会有一种圣杯般的药物来杀死衰老细胞。”尽管面临挑战,其他小组正在开始解开这个过程的各个部分。在他们自己的研究领域,成田博士和他的同事们正在试图阐明RAS癌基因是如何引发细胞衰老的。最初,批评者认为这种现象可能是实验室的人工产物,直到一系列研究在体内检测到它。在他们的研究中,成田博士和他的团队希望量化诱导衰老所需的RAS的大致生理剂量。根据他们和其他实验室的结果,成田博士推测,携带略高于正常致癌RAS水平的细胞可能会获得少量的生存益处。随着时间的推移,癌基因水平较高的细胞可能开始占据主导地位。然而,在某个时刻,这一水平将超过一个阈值;细胞应激会触发衰老的开始或导致细胞癌变。“因此,我们提出致癌衰老必须被视为一个光谱,然后才能成为肿瘤进化的一个组成部分,”他说。他说,与细胞分化一样,随着时间的推移,衰老可能会产生截然不同的基因表达谱。早期衰老的可塑性表明,处于这种过渡状态的细胞可能会癌变。成田博士说:“如果它衰老得很深,它可能就回不来了。我们不知道,没有人知道。”。他希望测试的一种可能性是,改变DNA染色质结构的表观遗传学机制可能最终导致衰老细胞达到不可逆转的地步。根据科学家对衰老进行阶段的发现,他们可能会更好地了解压力点在哪里,以及它们是否可以成为现实的目标。Martínez Zamudio博士说:“开发能够消除衰老细胞或调节衰老状态的药物有着巨大的推动力。”。他说,另一个重要的优先事项是生成一个关于衰老在不同情况下意味着什么的综合目录。在他自己的实验室里,他希望分析各种细胞类型和衰老诱导剂,看看驱动表型的因素是否有任何共性。根据他自己的一些研究,他认为AP1转录因子家族可能会监督一些重要的一般机制。成田博士说,研究领域正进入一个更加困难的阶段:然而,与发育过程中的细胞分化不同,他认为衰老过程更随机,或更不可预测。然而,就像Martínez Zamudio博士一样,他希望一些更大的模式可能会出现。如果是这样的话,这个领域可能正在朝着控制一个强大、危险、善变的细胞僵尸的方向发展。
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Cancer Cytopathology
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