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[Techniques and indications of neurosurgical treatment of oligometastatic renal cell carcinomas in case of spinal metastases]. 【脊柱转移少转移肾细胞癌的神经外科治疗技术及适应证】。
Q4 Medicine Pub Date : 2023-04-22
Tamás Tóth, Zoltán Mencser, Róbert Veres, Pál Barzó

The treatment of spinal metastases is a huge challenge, but both oncological and surgical treatment have improved significantly. Spine surgeons use the experience of spine surgeries performed for an increased number of degenerative causes during spine surgeries performed for an increased number of tumors. Establishing an indication for surgery is at least as much of a challenge as the surgery itself, for which there are many objective point systems available. Renal cell carcinoma metastases are less sensitive to radiation, which is why careful surgery is even more important. In our short summary, we review the symptoms, the examination, the grading systems used and the surgical options.

脊柱转移的治疗是一个巨大的挑战,但肿瘤和手术治疗都有显着改善。脊柱外科医生在为增加数量的肿瘤进行脊柱手术时,利用为增加数量的退行性原因进行脊柱手术的经验。建立手术指征至少和手术本身一样具有挑战性,因为有许多客观的点系统可用。肾细胞癌转移对辐射不太敏感,这就是为什么小心的手术更重要。在我们简短的总结中,我们回顾了症状,检查,使用的分级系统和手术选择。
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引用次数: 0
[Radiotherapy of kidney cancers: an allegory for changing approach in theory and practice]. [肾癌放射治疗:理论和实践方法变化的寓言]。
Q4 Medicine Pub Date : 2023-04-22
László Mangel

The evolution of radiotherapy (RT) technologies in the last two decades has changed the RT treatment attitude, and the routine application of novel stereotactic methods has opened new avenues in the complex cancer care. To prove the clinical consequences of this paradigm shift, a good example is the transformation of the renal cell carcinoma (RCC) treatment strategy. RCC was originally considered as a radioresistant disease, however, the introduction of new RT technologies has provided a risk-free focal dose escalation, so RT in primary or metastatic RCCs has become a more efficient method. Meanwhile, there has also been a spectacular development in the medical treatment of advanced RCC, thus the treatment strategy has radically changed in this field of oncology, resulting in a remarkably increased effectiveness. In the present communication, we summarize the steps of recent RT evolution, the new fields of indications and possibilities of combination therapies in RCC.

近二十年来放射治疗技术的发展改变了人们对放射治疗的态度,新型立体定向方法的常规应用为复杂的癌症治疗开辟了新的途径。为了证明这种范式转变的临床后果,一个很好的例子是肾细胞癌(RCC)治疗策略的转变。RCC最初被认为是一种放射耐药疾病,然而,新的放射治疗技术的引入提供了无风险的局灶剂量递增,因此原发性或转移性RCC的放射治疗已成为一种更有效的方法。与此同时,晚期肾细胞癌的医学治疗也有了惊人的发展,这一肿瘤学领域的治疗策略发生了根本性的变化,疗效显著提高。在本通讯中,我们总结了最近的RT发展的步骤,新的适应症领域和联合治疗的可能性在RCC。
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引用次数: 0
[Immune combination possibilities in the first-line treatment of metastatic renal cell cancer]. [免疫联合治疗转移性肾细胞癌一线治疗的可能性]。
Q4 Medicine Pub Date : 2023-04-22
Zsófia Küronya, Krisztina Biró, Lajos Géczi, Anikó Maráz

First-line treatment of metastatic renal cancer can be divided into three main phases. The cytokine era was replaced by targeted therapies in 2006 with the introduction of tyrosine kinase inhibitors. Until 2018, the standard first-line therapy was the use of sunitinib or pazopanib. Over the past decade, numerous attempts have been made to combine these drugs, which are already approved or in development, but these attempts have not been successful, primarily because of intolerable toxicity. In 2018, we reached a new stage in the treatment of metastatic renal tumors. This year, the combination immunotherapy of ipilimumab and nivolumab was approved. Since then, the combination of immunotherapy and targeted therapies has led to success. The main objective of our summary is to present in chronological order the clinical trials of combination therapies already approved in Europe, as well as the most recent phase III clinical trials. It is also intended to provide a brief practical guide on how to decide on first-line therapy based on the results of these trials.

转移性肾癌的一线治疗可分为三个主要阶段。2006年,随着酪氨酸激酶抑制剂的引入,细胞因子时代被靶向治疗所取代。直到2018年,标准的一线治疗是使用舒尼替尼或帕唑帕尼。在过去的十年里,已经有许多人尝试将这些药物结合起来,这些药物已经被批准或正在开发中,但这些尝试都没有成功,主要是因为难以忍受的毒性。2018年,我们在治疗转移性肾肿瘤方面达到了一个新的阶段。今年,ipilimumab和nivolumab联合免疫疗法获得批准。从那时起,免疫疗法和靶向疗法的结合取得了成功。我们总结的主要目的是按时间顺序介绍已经在欧洲批准的联合疗法的临床试验,以及最近的III期临床试验。它还旨在提供一个关于如何根据这些试验的结果决定一线治疗的简短实用指南。
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引用次数: 0
[Impact, and treatment possibility of chemotherapy resistance in cancer]. [癌症化疗耐药的影响及治疗可能性]。
Q4 Medicine Pub Date : 2023-04-22
Mihály Tamás Cserepes

Chemotherapy resistance in tumours is due to complex processes and is responsible for about half of all cancer deaths. In my thesis, I have investigated multiple different resistance mechanisms, most in depth the effect of multidrug resistance (MDR) caused by expression and function of P-glycoprotein (Pgp), and the MDR-selective compounds (such as NSC297366) effectively targeting it. The mechanism was investigated using cell models with different Pgp expression. Seeking the mechanism of action of the MDR-selective NSC297366, we showed that the intracellular iron-binding chelator molecule is able to reduce the amount of free iron available within the cell. Furthermore, by active efflux through Pgp in MDR cells, the compounds can lead to intracellular iron deficiency, upregulation of iron-demanding processes such as cell cycle and apoptosis, and selective death of MDR cancer cells. Our results raise the possibility of targeted killing of MDR phenotypic cancer cells resistant to other therapies, which in combination with conventional chemotherapeutic approaches may form the basis of a strategy of long-term control of the disease.

肿瘤的化疗耐药性是由于复杂的过程造成的,约有一半的癌症死亡是由化疗耐药性造成的。在我的论文中,我研究了多种不同的耐药机制,最深入的是p -糖蛋白(Pgp)的表达和功能引起的多药耐药(MDR)的影响,以及有效靶向它的耐药选择性化合物(如NSC297366)。通过不同Pgp表达的细胞模型研究其作用机制。为了寻找耐多药选择性NSC297366的作用机制,我们发现细胞内铁结合螯合剂分子能够减少细胞内可用的游离铁量。此外,通过Pgp在MDR细胞中的主动外排,这些化合物可导致细胞内缺铁,上调细胞周期和细胞凋亡等铁需求过程,以及MDR癌细胞的选择性死亡。我们的研究结果提高了靶向杀死耐多药表型癌细胞的可能性,这与传统的化疗方法相结合,可能形成长期控制该疾病的策略基础。
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引用次数: 0
[In vitro examination of N-methyl-D-aspartate type glutamate receptors in non-excitable cells]. [非兴奋细胞n-甲基- d -天冬氨酸型谷氨酸受体的体外检测]。
Q4 Medicine Pub Date : 2023-04-22
Tibor Hajdú

Our research was based on studies involving N-methyl- D-aspartate type glutamate receptors in chicken-derived differentiating chondrocytes, as well as in healthy and pathological human pigment cells. Given that NMDARs primarily mediate Ca2+ currents, we focused on the changes of Ca2+ homeostasis. The experiments proved that NMDARs may have roles in the precisely regulated intracellular Ca2+ oscillations of chondroprogenitor cells, and NMDAR-evoked Ca2+ signals are associated with optimal chondrogenesis. NMDAR subunit protein expression profiles in melanoma cells, involving subcellular fractions, revealed major differences between melanocytes and melanoma cells with potentially functional nuclear NMDARs in the latter. In summary we demonstrated in vitro, for the first time, in non-excitable cells from outside the nervous system the presence of functional NMDARs (in differentiating chondrocytes), and the nuclear localisation of NMDARs (in melanoma cells). The former mediate Ca2+-dependent pathways that are indispensable to chondrogenesis, while the latter may have appeared as a result of malignant transformation.

我们的研究是基于对鸡源性分化软骨细胞以及健康和病理人类色素细胞中n-甲基-d -天冬氨酸型谷氨酸受体的研究。鉴于NMDARs主要介导Ca2+电流,我们关注Ca2+稳态的变化。实验证明,NMDARs可能在软骨祖细胞胞内Ca2+振荡的精确调节中发挥作用,nmdar诱发的Ca2+信号与最佳软骨形成有关。NMDAR亚基蛋白在黑色素瘤细胞中的表达谱,包括亚细胞部分,揭示了黑素细胞和具有潜在功能的核NMDAR的黑色素瘤细胞之间的主要差异。总之,我们首次在体外证明了神经系统外不可兴奋细胞中功能性NMDARs的存在(在分化的软骨细胞中),以及NMDARs的核定位(在黑色素瘤细胞中)。前者介导的Ca2+依赖通路是软骨形成不可或缺的,而后者可能是恶性转化的结果。
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引用次数: 0
[Adjuvant treatment of kidney tumors - a more successful future?] 辅助治疗肾肿瘤-一个更成功的未来?]
Q4 Medicine Pub Date : 2023-04-22
Miklós Szűcs, János Szalontai, Péter Nyirády

Considering the data of the past years, the number of kidney tumor patients grows constantly. These patients are usually found incidentally with the help of common imaging procedures. The classic triad - lower back pain, bloody urine, and palpable flank terime - occurs rarely. Their presence foresees an advanced disease. In our article, in addition to the mentioning of the epidemiological and etiological data, symptoms, surgical therapy and histological types of the kidney tumors, we present the adjuvant treatment options, their types and effectiveness.

从过去几年的数据来看,肾肿瘤患者的数量在不断增长。这些患者通常是在普通影像学检查的帮助下偶然发现的。典型的三联征——腰痛、尿血和可触及的腹部疼痛——很少发生。它们的出现预示着一种晚期疾病。在我们的文章中,除了提到肾肿瘤的流行病学和病因学资料,症状,手术治疗和组织学类型外,我们还介绍了辅助治疗的选择,它们的类型和效果。
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引用次数: 0
[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. [基于真实世界数据的卡博赞替尼治疗转移性肾癌患者的多中心匈牙利结果]。
Q4 Medicine Pub Date : 2023-04-22
Anikó Maráz, Krisztián Nagyiványi, Ingrid Balogh, György Bodoky, László Mangel, Zsófia Küronya, Lajos Géczi, László Torday, Szilvia Dudás, Miklós Szűcs, Zsófia Nagy, Lajos Hornyák, Zita Zolcsák, Ali Bassam, Judit Kocsis, Tamás Keresztes, Tamás Kullmann, Károly Máhr, Tibor Solymosi, Tímea Papdán, Imre Szabó, Zoltán Varga, Krisztina Biró

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

我们分析的目的是评估卡博赞替尼对转移性肾细胞癌患者的疗效。2019年1月1日至2022年12月31日期间开始的Cabozantinib治疗基于对匈牙利14个肾脏中心数据的回顾性回顾进行了评估。起始剂量是60或40毫克。体格检查和实验室检查每4周进行一次,影像学检查每3个月进行一次。根据RECIST 1.1评估肿瘤反应,根据NCI CTCAE 4.0评估毒性。共评估230例患者记录,201例(87.4%)为透明细胞RCC。卡博赞替尼作为三线、二线和一线治疗的比例分别为48.7%、38.3%和48.7%
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引用次数: 0
[Could robotic surgery really be a revolutionary change in the treatment of kidney cancer in Hungary?] 机器人手术真的会成为匈牙利肾癌治疗的革命性变革吗?]
Q4 Medicine Pub Date : 2023-04-22
Norbert Fábián, Zalán Németh, Péter Tenke

Robotic-assisted partial nephrectomy (RAPN) was first described in 2004 and, since its introduction in clinical practice, has progressively gained increasing popularity. Over the years, the indications have also expanded, enabling robot-assisted surgical removal of complex kidney tumors. Important considerations for clinicians when choosing a minimally invasive technique are complete resection of the tumor, maximum protection of kidney function, and avoidance of complications. The first Da Vinci robotic surgery system was installed in Hungary at the Jahn Ferenc Dél- Pest Hospital and the National Institute of Oncology. The first robotic surgery took place at the National Institute of Oncology, and then at the Jahn Ferenc Dél-Pest hospital. In addition to open surgeries, only the laparoscopic procedure was available to perform kidney tumor surgeries in Hungary. The short one-year robotic surgery experience in our country supports the results of the international literature. Due to the introduction of robotics, a higher level of precision and freedom of movement creates new opportunities compared to open or laparoscopic kidney tumor surgeries.

机器人辅助部分肾切除术(RAPN)于2004年首次被描述,自其在临床实践中引入以来,已逐渐获得越来越多的普及。多年来,适应症也扩大了,使机器人辅助手术切除复杂的肾脏肿瘤成为可能。临床医生在选择微创技术时需要考虑的重要因素是完全切除肿瘤、最大限度地保护肾功能和避免并发症。第一个达芬奇机器人手术系统安装在匈牙利的Jahn Ferenc dassil - Pest医院和国家肿瘤研究所。第一个机器人手术是在国家肿瘤研究所进行的,然后是在Jahn Ferenc dsaml - pest医院。在匈牙利,除了开放手术,只有腹腔镜手术可以进行肾肿瘤手术。我国短短一年的机器人手术经验支持了国际文献的研究结果。由于机器人技术的引入,与开放或腹腔镜肾肿瘤手术相比,更高水平的精度和运动自由创造了新的机会。
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引用次数: 0
[Pathological characteristics and genetic background of renal cell carcinoma]. 【肾细胞癌的病理特点及遗传背景】。
Q4 Medicine Pub Date : 2023-04-22
Fanni Sánta, Boglárka Pósfai, Anita Sejben, Levente Kuthi

Renal cell carcinoma (RCC) is the most common malignant kidney tumor. It is not a single entity but an umbrella term for several distinct tumor types. The most prevalent and clinically significant subtype of RCC is clear cell carcinoma, which consists of cells with empty cytoplasm. These tumor cells harbor biallelic loss of the VHL gene, resulting in a pseudohypoxic state that promotes angiogenesis and cellular proliferation. Papillary RCC and chromophobe carcinoma are also common subtypes, with the former displaying a papillary appearance and cMET mutation. The latter is characterized by eosinophilic tumor cells and multiple chromosomal losses. These subtypes are responsible for 90-95% of all kidney cancers in adults. Additionally, rare tumor subtypes with unique immunohistochemical features, genetic abnormalities, or a specific clinical course may be identified. Currently, the RCC subtype only holds prognostic significance, and no treatment is associated with any subtype. However, therapies associated with histological subtypes may emerge in the future, and thus, the diagnosis of RCCs should be made following current recommendations.

肾细胞癌(RCC)是最常见的恶性肾脏肿瘤。它不是一个单一的实体,而是几种不同肿瘤类型的总称。最常见和临床意义的RCC亚型是透明细胞癌,它由细胞质空的细胞组成。这些肿瘤细胞含有VHL基因双等位基因缺失,导致假性缺氧状态,促进血管生成和细胞增殖。乳头状RCC和嫌色癌也是常见的亚型,前者表现为乳头状外观和cMET突变。后者的特点是嗜酸性肿瘤细胞和多染色体丢失。这些亚型导致了90-95%的成人肾癌。此外,罕见的肿瘤亚型具有独特的免疫组织化学特征,遗传异常,或特定的临床过程可以确定。目前,RCC亚型仅具有预后意义,没有与任何亚型相关的治疗。然而,与组织学亚型相关的治疗方法可能会在未来出现,因此,rcc的诊断应遵循目前的建议。
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引用次数: 0
[Second and further lines treatment options for locally advanced or metastatic renal cell carcinoma]. [局部晚期或转移性肾细胞癌的二线和进一步治疗方案]。
Q4 Medicine Pub Date : 2023-04-22
Krisztián Nagyiványi, Lajos Géczi

The treatment of locally advanced, inoperable or metastatic kidney tumors is a dynamically changing field of oncology. Since the registration of the first targeted therapeutic product (2005), more and more new products have been internationally accepted and registered almost every year. The development of immune checkpoint inhibitors and their inclusion in care algorithms (2015) further expanded the therapeutic possibilities. Despite all this, the optimal selection of medication used in different therapeutic lines poses a significant challenge to clinicians. In this review we have collected the data, aspects, and results of clinical tests necessary for the choice of therapy that can be applied in second and further lines. We also present the domestic treatment options.

局部晚期、不能手术或转移性肾肿瘤的治疗是肿瘤学一个动态变化的领域。自第一个靶向治疗产品(2005年)注册以来,几乎每年都有越来越多的新产品在国际上被接受和注册。免疫检查点抑制剂的发展及其纳入护理算法(2015年)进一步扩大了治疗的可能性。尽管如此,在不同的治疗线中使用药物的最佳选择对临床医生提出了重大挑战。在这篇综述中,我们收集了临床试验的数据、方面和结果,以选择可应用于二线和二线的治疗方法。我们还介绍了国内治疗方案。
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引用次数: 0
期刊
Magyar onkologia
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