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Tumor tissue samples collection for scientific research in morphology and molecular oncology 为形态学和分子肿瘤学科学研究收集肿瘤组织样本
Pub Date : 2024-02-19 DOI: 10.17709/2410-1893-2024-11-1-3
O. R. Khabarov, B. D. Seferov, K. A. Aliev, D. Zima, E. Golubinskaya, E. Zyablitskaya
Purpose of the study. Is to describe the experience of creating a collection of biological images of tumor tissues and biomaterials, which are control samples, for scientific research in morphology and molecular oncology.Materials and methods. We studied the molecular markers of cell cycle regulation, apoptosis, oncogenesis and angiogenesis, the expression of proteins that regulate inflammation and tumor infiltrate cells in biocollections of verified tumors of common localizations: e. g. thyroid cancer, colorectal cancer, breast cancer, prostate adenocarcinoma, endometrioid adenocarcinoma. Also, tissue fragments with normal structure or non-tumor pathology (autoimmune thyroiditis, adenomatous and thyrotoxic goiter, benign formations of the colon, fibrocystic disease of the mammary glands, benign prostatic hyperplasia, endometrial hyperplasia) were used as control samples or comparison groups. The total number of tissue samples is n = 7000.Results. It is reasonable to gather the collection in a pathomorphological laboratory according to the profile of the medical institutions, which has a sufficient volume of incoming target material and specialized morphologists to verify tumors of a given localization. It is necessary to consider the regional and ethnic specifics of the population, which determines the sampling and mutational load. The laboratory must initiate an addition to the informed consent of patients about the possibility of conducting morphological and molecular genetic studies for scientific purposes and publishing their results in a depersonalized form for the development of new elaborations, when signing the contracts with legal entities and individuals and when serving patients within an institution. When working with biocollections, it has to consider having registers of tissue biomaterials of target disorder groups of main localizations with downloading by year from an accessible information system, consider external factors affecting the database (changes in clinical recommendations and classifications, the population of patients served, pandemics and other significant events). The standard of the preanalytical stage, data collection, development of protocols for analytical molecular genetic studies and their evaluation, the utilization of the capabilities of working with reagents for scientific tasks and modeling experiments on laboratory animals are crucial.Conclusion. The formed biocollection made it possible to carry out a number of initiative and funded domestic and international scientific projects at the request of clinicians and fundamental researchers, as well as to improve the quality standards of morphological and molecular genetic oncology diagnostics. Biobanking makes the pathological archive more accessible for review and use, significantly expanding its scientific and practical potential. Scientific and medical research do not conflict and can be used within the same laboratory.
研究目的描述为形态学和分子肿瘤学科学研究建立肿瘤组织和生物材料(作为对照样本)生物图像集合的经验。我们研究了甲状腺癌、结直肠癌、乳腺癌、前列腺腺癌、子宫内膜样腺癌等常见部位已证实肿瘤的生物图像集中细胞周期调节、细胞凋亡、肿瘤发生和血管生成的分子标记物,以及调节炎症和肿瘤浸润细胞的蛋白质表达。此外,结构正常或无肿瘤病变的组织片段(自身免疫性甲状腺炎、腺瘤性和甲状腺肿、结肠良性病变、乳腺纤维囊性疾病、良性前列腺增生、子宫内膜增生)也被用作对照样本或对比组。组织样本总数为 n = 7000。根据医疗机构的情况,在病理形态学实验室收集样本是合理的,因为病理形态学实验室有足够数量的目标材料和专门的形态学专家来验证特定定位的肿瘤。有必要考虑人口的地区和种族特点,这决定了取样和突变负荷。实验室在与法人实体和个人签订合同时,以及在为机构内的患者提供服务时,必须在患者知情同意书中增加一项内容,即为科学目的进行形态学和分子遗传学研究的可能性,并以非人格化的形式公布研究结果,以便进行新的阐述。在进行生物收集工作时,必须考虑建立主要地区目标疾病群体的组织生物材料登记册,并从可访问的信息系统中按年下载,还要考虑影响数据库的外部因素(临床建议和分类的变化、服务的病人群体、流行病和其他重大事件)。分析前阶段的标准、数据收集、分子遗传分析研究方案的制定及其评估、利用试剂完成科学任务的能力以及对实验动物进行建模实验都至关重要。已形成的生物收集使我们有可能应临床医生和基础研究人员的要求,开展一些主动的、有资金支持的国内和国际科学项目,并提高肿瘤形态学和分子遗传学诊断的质量标准。生物库使病理档案更易于查阅和使用,极大地拓展了其科学和实用潜力。科学研究和医学研究并不冲突,可在同一实验室内使用。
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引用次数: 0
The effect of the relative dose intensity of chemoradiotherapy on the effectiveness of therapy of locally advanced unresectable non-small cell lung cancer 化放疗的相对剂量强度对局部晚期不可切除非小细胞肺癌疗效的影响
Pub Date : 2024-02-19 DOI: 10.17709/2410-1893-2024-11-1-2
A. E. Glukhareva, G. V. Afonin, I. Kolobaev, L. Grivtsova, S. A. Ivanov, A. Kaprin
The purpose of the study. To estimate the number of patients with the preservation of relative dose intensity (RDI) ≥ 80 % of first-line antitumor therapy in patients with unresectable non-small cell lung cancer (NSCLC), and to compare the effectiveness of therapy in groups with optimal and lower RDI.Patients and methods. The study included 30 patients (25 men and 5 women) with locally advanced unresectable NSCLC. The median age was 57 years. The main criterion for inclusion in the study was morphologically verified NSCLC with stage IIIB-IIIC of the disease. All patients underwent simultaneous chemoradiotherapy. According to the histogenesis of the tumor process, patients with a squamous cell variant prevailed.Results. The data obtained from 22 (73.3 %) patients who retained a relative dose intensity of RDI > 80 % demonstrated that given dose intensity is sufficient to achieve a stable antitumor effect. In 8 (26.7 %) cases, however, the RDI was less than 80 %, which affected the effectiveness of the treatment. The median follow-up for overall survival (OS) was 29.2 months, progression-free survival (PFS) was 15.1 months, and local control was 21.9 months. in all patients included in the analysis. The indicators of OS in the second year had an advantage in the group of patients with RDI < 80 % and amounted to 73.3 % compared with 60.5 % in patients with RDI > 80 %. PFS was higher in the group of patients with high dose intensity, in the first year of follow-up it was 75.6 % compared with the group of patients with RDI < 80 % (62.5 %), in the second year of follow-up, PFS was 27.2 % and 20.8 %, respectively. Local control was 90.2 % in the first year in the group of patients with RDI > 80 % and 62.5 % in the group of patients with RDI < 80 %. The second year of follow-up demonstrated the advantage of the group of patients with RDI >80 % in terms of local control and amounted to 48.1 % versus 34.7 %, respectively.Conclusion. The results obtained show that maintaining relative dose intensity at a high level has a positive effect on survival rates and local control of patients with locally advanced unresectable NSCLC. However, there is a cohort of patients who did not receive the planned amount of treatment, due to the high toxicity of simultaneous chemoradiotherapy. It is necessary to develop new approaches to concomitant therapy aimed at reducing the toxicity of the combined treatment and achieving maximum antitumor effect.
研究目的估算不可切除非小细胞肺癌(NSCLC)患者一线抗肿瘤治疗中保留相对剂量强度(RDI)≥80%的患者人数,并比较最佳和较低RDI组的治疗效果。研究纳入了30名局部晚期不可切除NSCLC患者(25名男性和5名女性)。中位年龄为 57 岁。纳入研究的主要标准是经形态学证实的 NSCLC IIIB-IIIC 期患者。所有患者均接受了同步放化疗。根据肿瘤的组织发生过程,鳞状细胞变异患者居多。22例(73.3%)患者的相对剂量强度(RDI)大于80%,这些数据表明,给定的剂量强度足以达到稳定的抗肿瘤效果。然而,有 8 例(26.7%)患者的相对剂量强度低于 80%,影响了治疗效果。在所有纳入分析的患者中,总生存期(OS)的中位数为 29.2 个月,无进展生存期(PFS)为 15.1 个月,局部控制为 21.9 个月。第二年的OS指标在RDI<80%的患者组中更具优势,达到73.3%,而在RDI>80%的患者中为60.5%。高剂量强度组患者的 PFS 更高,随访第一年的 PFS 为 75.6%,而 RDI < 80% 组为 62.5%,随访第二年的 PFS 分别为 27.2% 和 20.8%。在第一年的随访中,RDI > 80% 组患者的局部控制率为 90.2%,RDI < 80% 组患者的局部控制率为 62.5%。在第二年的随访中,RDI>80%的患者组在局部控制方面更具优势,分别达到48.1%和34.7%。研究结果表明,保持较高的相对剂量强度对局部晚期不可切除 NSCLC 患者的生存率和局部控制率有积极影响。然而,由于同步放化疗的高毒性,有一部分患者没有接受计划的治疗量。因此,有必要开发新的同步治疗方法,以减少联合治疗的毒性,达到最大的抗肿瘤效果。
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引用次数: 0
Ultrasound cases of an elongated left lobe of the liver as an anatomical variant 作为解剖变异的肝左叶拉长的超声病例
Pub Date : 2024-02-19 DOI: 10.17709/2410-1893-2024-11-1-7
N. V. Ischenko, N. K. Vinogradova, L. A. Titova, E. M. Tolstykh, S. I. Marks
The elongated left lobe of the liver (saddle liver, saber liver, beaver tail liver, beaver lobe) is one of the types of variant liver anatomy, characterized by the fact that the left lobe extends far beyond the midline of the body, and can come into contact with the spleen and even go above it. Due to the fact that the elongated left lobe of the liver is more often susceptible to injury and, in some cases, can imitate a subcapsular hematoma of the spleen, it seems important to increase the awareness among doctors of various specialties about the variety of morphological variations in the structure of the liver, in particular about the elongated left lobe of the liver, to unify approaches to the description and establish uniformity of wording to designate this feature of the anatomical structure of the left lobe of the liver, which will reduce the risk of diagnostic errors and errors during surgical interventions, especially in cases of blunt abdominal trauma.The article presents clinical cases with ultrasound examination of 10 patients of different ages (from 1 month to 38 years) and gender with a newly diagnosed anomaly in the structure of the left lobe of the liver, i.e an elongated left lobe. An analysis of national and foreign literature sources containing reports on various morphological variants of the liver structure and the frequency of their occurrence was carried out. Ultrasound signs were proposed to describe the elongated left lobe of the liver. The features of the ultrasound examination technique for the elongated left lobe of the liver in children older than one year are described. The variety of formulations used by different authors when describing this variant of the anatomical structure of the liver was studied.
拉长的肝左叶(马鞍肝、马刀肝、海狸尾肝、海狸叶)是变异肝脏解剖类型之一,其特点是肝左叶远远超出身体中线,可与脾脏接触,甚至高于脾脏。由于拉长的肝左叶更容易受到损伤,在某些情况下还会模仿脾脏的囊下血肿,因此提高各科医生对肝脏结构中各种形态变异的认识显得尤为重要、因此,提高各科医生对肝脏结构中各种形态变化的认识,尤其是对肝左叶伸长的认识,统一描述方法,确定统一的措辞来描述肝左叶解剖结构的这一特征,这将减少诊断错误和手术干预过程中出错的风险,尤其是在腹部钝性创伤的病例中。文章通过对 10 例不同年龄(从 1 个月到 38 岁)和性别的新诊断肝左叶结构异常(即左叶变长)患者的超声检查,介绍了临床病例。我们对国内外有关肝脏结构各种形态变异及其发生频率的文献资料进行了分析。提出了描述肝左叶变长的超声征象。描述了一岁以上儿童肝左叶变长的超声检查技术特点。研究了不同作者在描述这种肝脏解剖结构变异时使用的各种说法。
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引用次数: 0
The organ sparing management of a patient with urachus cancer in conditions of comorbidity 在合并症情况下对尿道癌患者进行器官切除治疗
Pub Date : 2024-02-16 DOI: 10.17709/2410-1893-2024-11-1-6
M. Ter-Ovanesov, D. M. Yagudaev, A. Gritskevich, A. V. Umyarova, V. A. Bezhenar
Malignant tumors of the urachus are extremely rare. The frequency of urachal malignancy makes 1: 5 000 000 cases, which is 0.35–1.2 % of all the cases of bladder cancer. The small series of observations described in the literature do not allow us to formulate statistically reliable and unambiguously recommended statements about the optimal methods of diagnostics and treatment of this pathology. The diagnosis of urachus diseases is often challenging. This is associated with both the asymptomatic course and the variety of clinical flow of the disease. The treatment strategies are also largely ambiguous and ranging from the defining the indications for surgical treatment to the aggressiveness of surgical intervention. Meanwhile, 20 % of patients with urachal cancer have distant metastases at the time of detection. With everything listed above, (low frequency, little research done and aggressiveness of the flow) it makes every clinical observation of this disease valuable.This article is a clinical observation providing with the information upon the diagnosis, the choice of strategies and surgical treatment of urachal cancer in a patient suffering from multimorbidity. Volumetric formation of the bladder was detected in this patient during additional examination for macrohematuria. Cystoscopy with transurethral resection and subsequent morphological examination verified invasive mucinous adenocarcinoma of the bladder with the growth into the lamina propria and without the signs of vascular and perineural invasion. The patient underwent laparotomy, radical resection of the bladder with extended pelvic lymphadenectomy. The umbilicus, urachus and the bladder wall with the tumor, as well as the adjacent peritoneum, were excised as a single block during the surgical intervention. Morphological examination verified mucinous adenocarcinoma of urachus. The postoperative period was uneventful.There have been no signs of disease progression observed during 10-month follow-up period.
尿道恶性肿瘤极为罕见。膀胱恶性肿瘤的发病率为 1:5000000,占所有膀胱癌病例的 0.35-1.2%。文献中描述的少量观察结果无法让我们对该病症的最佳诊断和治疗方法做出可靠的统计和明确的建议。尿道疾病的诊断通常具有挑战性。这与该病的无症状病程和临床表现多种多样有关。治疗策略在很大程度上也是模糊的,从手术治疗适应症的确定到手术干预的积极性。同时,20% 的泌尿道癌患者在发现时已有远处转移。鉴于上述情况(发病率低、研究成果少、血流凶险),对这种疾病的每一次临床观察都很有价值。本文是一篇临床观察报告,提供了对一名患有多种疾病的患者进行膀胱癌诊断、策略选择和手术治疗的信息。该患者在大血尿的补充检查中发现膀胱体积增大。膀胱镜检查和经尿道切除术以及随后的形态学检查证实,膀胱浸润性粘液腺癌向固有层生长,没有血管和神经周围侵犯的迹象。患者接受了开腹手术、膀胱根治性切除术和盆腔淋巴结扩大切除术。在手术过程中,脐部、尿道、膀胱壁和肿瘤以及邻近的腹膜被一并切除。形态学检查证实为尿道粘液腺癌。术后恢复顺利,10 个月的随访期间未发现疾病进展迹象。
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引用次数: 0
Extracellular mitochondria as promising diagnostic agents 细胞外线粒体是前景广阔的诊断剂
Pub Date : 2024-02-16 DOI: 10.17709/2410-1893-2024-11-1-4
О. I. Kit, E. Frantsiyants, A. Shikhlyarova, I. V. Neskubina, S. A. Ilchenko
Nowadays, there is a new concept that says that mitochondria naturally circulate in the blood and this is characteristic of both human and animal bodies. It is believed that circulating mitochondria can easily pass through tissue barriers due to their small size (50–400 nm). The phenomenon of mitochondrial intercellular transfer, which is bidirectional, has been observed in vitro and in vivo, under both physiological and pathophysiological conditions, and among a variety of cells, including malignant tumor cells. Circulating cell-free intact mitochondria are thought to play an active biological and physiological role, as mitochondria are already known to be systemic mediators of intercellular communication, transmitting hereditary and non-hereditary biological components, including MtDN A. Mitochondrial components of cellular origin, including mitochondrial DNA, were detected in the extracellular space. There are about 50,000 times more copies of the mitochondrial genome than the nuclear genome in the blood plasma of healthy people. The researchers confirmed that mitochondrial cell-free DNA (McfDNA) is stable enough for detection and quantification, implying that there are stable structures protecting these DNA molecules. The circulating mitochondrial genome, which is released as a cell-free mitochondrial DNA, is recognized as a new biomarker of mitochondrial stress and signal transduction. McfDNA has become an attractive circulating biomarker because of its potential use in diagnostic programs for various diseases, e. g., diabetes, acute myocardial infarction, and cancer. There is no doubt that detection of circulating mitochondria and their DNA in body fluids opens up a new promising scientific direction in biology and medicine. The article analyzes modern scientific data devoted to proving the existence of extracellular mitochondria, their functions outside the cell and diagnostic value.
如今,有一种新的观点认为,线粒体在血液中自然循环,这是人类和动物身体的特征。人们认为,循环中的线粒体由于体积小(50-400 纳米),很容易穿过组织屏障。在体外和体内,在生理和病理生理条件下,以及在包括恶性肿瘤细胞在内的各种细胞之间,都观察到了线粒体的细胞间转移现象,这种转移是双向的。循环中的无细胞完整线粒体被认为发挥着积极的生物学和生理学作用,因为线粒体已被认为是细胞间通信的系统介质,可传递遗传和非遗传的生物成分,包括 MtDN A,在细胞外空间检测到细胞来源的线粒体成分,包括线粒体 DNA。在健康人的血浆中,线粒体基因组的拷贝数约为核基因组的 5 万倍。研究人员证实,无细胞线粒体 DNA(McfDNA)足够稳定,可以进行检测和定量,这意味着存在稳定的结构保护这些 DNA 分子。作为无细胞线粒体 DNA 释放的循环线粒体基因组被认为是线粒体压力和信号转导的新生物标志物。McfDNA 已成为一种有吸引力的循环生物标志物,因为它有可能用于各种疾病(如糖尿病、急性心肌梗塞和癌症)的诊断项目。毫无疑问,检测体液中的循环线粒体及其 DNA 为生物学和医学开辟了一个新的科学方向。文章分析了致力于证明细胞外线粒体的存在、其在细胞外的功能和诊断价值的现代科学数据。
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引用次数: 0
Radiomics and radiogenomics in intrahepatic cholangiocarcinoma 肝内胆管癌的放射组学和放射基因组学
Pub Date : 2024-02-16 DOI: 10.17709/2410-1893-2024-11-1-5
A. D. Smirnova, G. G. Karmazanovsky, E. Kondratyev, N. Karelskaya, V. Galkin, A. Y. Popov, B. Gurmikov, D. Kalinin
Purpose of the study. Analytical review and analysis of available literature on texture analysis of computed tomgraphy (CT) and magnetic resonance imaging (MRI) in noninvasive diagnosis of ICC and correlation with molecular genetic features and tumor immunophenotype.Materials and methods. The scientific publications and clinical guidelines in the information- analytical systems PubMed, Scopus for 2012–2022 were carried out using the keywords: "mri", "radiomics", "texture analysis", "radiogenomics", "intrahepatic cholangiocarcinoma", "molecular". 49 articles were selected for analysis after excluding studies dealing with technical aspects of radiomics and describing individual clinical observations.Results. The presented review demonstrated the broad possibilities and prospects of application of CT and MRI texture analysis in the study of cholangiocellular cancer, including the first results in the study of molecular features (signatures) of this tumor. Correlation of texture features with the expression of immunotherapy target genes KRAS/NRAS/BRAF as well as IDH1/2 mutation was shown. Texture scores were the predominant independent predictor of microvascular invasion, which was a major independent risk factor for postoperative recurrence.Conclusion. The use of texture analysis undoubtedly demonstrates promising possibilities both in noninvasive assessment of the HCC histological differentiation grade, as well as in differential diagnosis with hepatocellular carcinoma, metastases, and requires further study for systematization and standardization of the obtained data.
研究目的分析综述和现有文献中关于计算机断层扫描(CT)和磁共振成像(MRI)在ICC无创诊断中的纹理分析以及与分子遗传特征和肿瘤免疫表型的相关性。使用关键词 "MRI"、"radioomom "和 "CT",在信息分析系统PubMed和Scopus中搜索2012-2022年的科学出版物和临床指南:"mri"、"radiomics"、"texture analysis"、"radiogenomics"、"intrahepatic cholangiocarcinoma"、"molecular"。在排除了涉及放射组学技术方面的研究和描述个别临床观察结果的研究后,选出 49 篇文章进行分析。综述展示了 CT 和 MRI 纹理分析在胆管细胞癌研究中应用的广泛可能性和前景,包括该肿瘤分子特征(特征)研究的首批成果。纹理特征与免疫疗法靶基因KRAS/NRAS/BRAF的表达以及IDH1/2突变之间存在相关性。纹理评分是微血管侵犯的主要独立预测指标,而微血管侵犯是术后复发的主要独立风险因素。纹理分析的使用无疑为无创评估 HCC 组织学分化等级以及鉴别诊断肝细胞癌和转移灶提供了可能,但还需要进一步研究,以实现所获数据的系统化和标准化。
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引用次数: 0
Safety assessment of preventive pressurized intraperitoneal aerosol chemotherapy in combined treatment of gastric cancer: preliminary results 预防性加压腹腔内气溶胶化疗在胃癌联合治疗中的安全性评估:初步结果
Pub Date : 2024-02-16 DOI: 10.17709/2410-1893-2024-11-1-1
N. Y. Muratova, I. Kolobaev, D. Kudryavtsev, E. Smolenov, A. Ryabov, V. Khomyakov, L. Petrov, S. A. Ivanov, A. Kaprin
Purpose of the study. Preventive pressurised intraperitoneal aerosol chemotherapy (PIPAC) safety assessment in the combined treatment of gastric cancer (GC).Patients and methods. The study included 48 patients with morphologically confirmed resectable GC and cardio esophageal transition, having at least one criterion that is a predictor of the development of peritoneal carcinomatosis, e. g. tumor spread to the serous layer (≥ T4a), diffuse tumor type, affected regional lymph nodes, large tumor, young age (up to 45 years), subtotally and totally affected stomach. 36 out of those patients received treatment according to the protocol. All patients received 4 cycles of neoadjuvant chemotherapy according to the FLOT scheme, radical surgical treatment in combination with a PIPAC session, 4 cycles of adjuvant chemotherapy according to the FLOT scheme. The safety assessment was carried out according to the classification of surgical complications according to Clavien-D indo and the international scale for toxicity scaling NCI–CTCAE v5.0.Results. Postoperative complications were diagnosed in 25 %, >III grade complications were revealed in 11 % of cases according to the Clavien-D indo classification. The postoperative mortality rate was 0 %.Conclusion. Preventive PIPAC of locally advanced GC and CET in combined treatment is a reproducible and safe method, which is characterized by the absence of an increase in the number of postoperative complications and mortality rate.
研究目的。对联合治疗胃癌(GC)的预防性腹腔内加压气溶胶化疗(PIPAC)进行安全性评估。研究纳入了48名形态学确诊为可切除胃癌和贲门食管转移的患者,这些患者至少具备一项可预测腹膜癌变发生的标准,如肿瘤扩散至浆液层(≥T4a)、弥漫性肿瘤类型、区域淋巴结受累、肿瘤较大、年龄较小(45岁以下)、胃次全受累和全受累。其中36名患者按照方案接受了治疗。所有患者均按照FLOT方案接受了4个周期的新辅助化疗、根治性手术治疗和PIPAC治疗,并按照FLOT方案接受了4个周期的辅助化疗。根据Clavien-D indo的手术并发症分类和NCI-CTCAE v5.0国际毒性评分标准进行了安全性评估。根据Clavien-D indo的分类,25%的病例被诊断出术后并发症,11%的病例并发症超过III级。术后死亡率为0%。对局部晚期GC和CET进行预防性PIPAC联合治疗是一种可重复的安全方法,其特点是不会增加术后并发症的数量和死亡率。
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