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26Жамият ва инновациялар -Общество и инновации -Society and innovations
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General information about childhood kidney tumors (nefroblastoma)
Daniyar NISHANOV1, Ramon MATRASULOV2
Specialized Scientific and Practical Medical Center of Oncology and Radiology Urgench Branch of the Tashkent Medical Academy
ARTICLE INFO
ABSTRACT
Article history:
Received June 2021 Received in revised form 20 June 2021 Accepted 15 July 2021 Available online 15 August 2021
Keywords:
nephroblastoma, tumors in childhood, nephroblastoma in children, incidence of nephroblastoma in childhood, malignant tumors, epidemiology of nephroblastoma.
Nephroblastoma is a high-risk embryonic tumor that arises from the developing kidney tissue. The disease is a common malignant tumor of the urogenital tract in children under 5 years of age and occurs equally in boys and girls. The relationship between the mother's age and the likelihood of having a baby with Wilms nephroblastoma can often be accompanied by birth defects. For nephroblastoma, hematogenous and lymphogenous metastases are characteristic, and lymphogenous metastases occur early. Most often, the lymph nodes located in the region of the portal renal, para-aortic and hepatic gates are affected. Hematogenously, they mainly metastasize to the lungs, less often to the liver.
2181-1415/© 2021 in Science LLC.
This is an open access article under the Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/deed.ru)
Болалардаги буйрак усмалари хэцида умумий маълумотлар (нефробластома)
Калит сузлар:
нефробластома, болаликдаги усма, болалардаги нефробластома, болаликдаги
нефробластома частотаси, хавфли усмалар, нефробластома эпидемиологияси.
АННОТАЦИЯ
Нефробластома - бу ю;ори хавфлиликка эга булган эмбрионал усма булиб, буйракнинг ривожланаётган ту;ималаридан келиб чи;ади. Касаллик 5 ёшгача булган болаларда сийдик-таносил трактининг кенг тар;алган хавфли усмаси булиб, угил болалар ва ;из болаларда бир хилда тар;алган булади. Бу касаллик онанинг ёши ва болани Вильмс нефробластомаси билан тугилиш эхтимоли орасидаги муносабатлар купинча тугма ну;сонлар билан бирга келиши мумкин. Нефробластома учун гематоген ва
1 Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology, Tashkent, Uzbekistan.
2 Urgench Branch of the Tashkent Medical Academy, Urgench, Uzbekistan.
Жамият ва инновациялар - Общество и инновации - Society and innovations Special Issue - 7 (2021) / ISSN 2181-1415
лимфоген метастазланиш хос булиб, лимфоген метастазланиш эрта юзага келади. Купинча буйрак дарвозаси, парааортал ва жигар дарвоза сох,асида жойлашган лимфа тугунлар жарох,атланади. Гематоген метастазланиш х,олатлари асосан упкага, кам х,олларда жигарга метастаз беради.
Общая информация о детских опухолях почек (нефробластома)
АННОТАЦИЯ_
Нефробластома - это эмбриональная опухоль высокого риска, которая возникает из развивающейся ткани почки. Заболевание представляет собой распространенную злокачественную опухоль урогенитального тракта у детей до 5 лет и в равной степени встречается у мальчиков и девочек. Связь между возрастом матери и вероятностью рождения ребенка с нефробластомой Вильмса часто может сопровождаться врожденными дефектами. Гематогенные и лимфогенные метастазы характерны для нефробластомы, а лимфогенные метастазы возникают рано. Чаще всего поражаются лимфатические узлы, расположенные в области воротного почечного, парааортального и печеночного ворот. Гематогенным путем в основном метастазируют в легкие, реже - в печень.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50% [1]. For children younger than 15 years with Wilms tumor, the 5-year survival rate has increased over the same time from 74% to 88% [12]. Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment.
Childhood kidney cancers account for about 7% of all childhood cancers. Most childhood kidney cancers are Wilms tumor, but in the 15- to 19-year age group, most tumors are renal cell carcinoma. Wilms tumor can affect one kidney (unilateral) or both kidneys (bilateral). Less common types of childhood kidney tumors include rhabdoid tumors, clear cell sarcoma, congenital mesoblastic nephroma, Ewing sarcoma of the kidney, primary renal myoepithelial carcinoma, cystic partially differentiated nephroblastoma, multilocular cystic nephroma, primary renal synovial sarcoma, and anaplastic sarcoma. Nephroblastomatosis of the kidney is a type of nonmalignant neoplasia [23].
Wilms tumor is the most frequent tumor of the kidney in infants and children. The incidence of Wilms tumor is 8.2 cases for every 1 million children younger than 15 years, or one case per 10,000 infants [1]. Approximately 650 cases of Wilms tumor are diagnosed in the United States each year. The incidence is substantially lower in Asians [12, 27].
The male to female ratio in unilateral cases of Wilms tumor is 0.92 to 1.00, but in bilateral cases, it is 0.60 to 1.00. The mean age at diagnosis is 44 months in unilateral cases and 31 months in bilateral cases of Wilms tumor [11, 25] About 10% of children with Wilms tumor have an associated congenital malformation syndrome [18].
Ключевые слова:
нефробластома, опухоли в детском возрасте,
нефробластома у детей, частота нефробластомы в детском возрасте, злокачественные опухоли, эпидемиология нефробластомы.
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Wilms tumor is the most frequent tumor of the kidney in infants and children. The incidence of Wilms tumor is 8.2 cases for every 1 million children younger than 15 years, or one case per 10,000 infants.[12] Approximately 650 cases of Wilms tumor are diagnosed in the United States each year. The incidence is substantially lower in Asians [27].
The male to female ratio in unilateral cases of Wilms tumor is 0.92 to 1.00, but in bilateral cases, it is 0.60 to 1.00. The mean age at diagnosis is 44 months in unilateral cases and 31 months in bilateral cases of Wilms tumor. About 10% of children with Wilms tumor have an associated congenital malformation syndrome. [11, 25].
Wilms tumor typically develops in otherwise healthy children without any predisposition to developing cancer; however, approximately 10% of children with Wilms tumor have been reported to have a congenital anomaly [17, 18]. In patients with congenital anomalies and Wilms tumor, nephrogenic rests have been reported in 60% of cases. Of 295 consecutive patients with Wilms tumor seen at the Institut Curie in Paris, 52 (17.6%) had anomalies or syndromes, 43 of which were considered major, and 14 of which were genetically proven tumor predisposition syndromes [19].
Wilms tumor may arise during embryogenesis on the background of an otherwise genomically normal kidney, or it may arise from nongermline somatic genetic precursor lesions residing in histologically and functionally normal kidney tissue. Hypermethylation of H19, a known component of a subset of Wilms tumors, is a very common genetic abnormality found in these normal-appearing areas of precursor lesions [21].
One study performed genome-wide sequencing, mRNA and miRNA expression, DNA copy number, and methylation analysis on 117 Wilms tumors followed by targeted sequencing of 651 Wilms tumors. The tumors were selected for either favorable histology (FH) Wilms that had relapsed or those with diffuse anaplasia. The study showed the following: Wilms tumors commonly arise through more than one genetic event, Wilms tumors show differences in gene expression and methylation patterns with different genetic aberrations, Wilms tumors have a large number of candidate driver genes, most of which are mutated in less than 5% of Wilms tumors, Wilms tumors have recurrent mutations in genes with common functions, with most involved in either early renal development or epigenetic regulation (e.g., chromatin modifications, transcription elongation, and miRNA) [2].
Approximately one-third of Wilms tumor cases involve mutations in WT1, CTNNB1, or WTX. [13, 20] Another subset of Wilms tumor cases results from mutations in miRNA processing genes (miRNAPG), including DROSHA, DGCR8, DICER1, and XPO5. [6, 9, 22, 29]. Other genes critical for early renal development that are recurrently mutated in Wilms tumor include SIX1 andSIX2 (transcription factors that play key roles in early renal development) [9, 29.] Of the mutations in Wilms tumors, 30% to 50% appear to converge on the process of transcriptional elongation in renal development and include the genesMLLT1, BCOR, MAP3K4, BRD7, and HDAC4 [2]. Anaplastic Wilms tumor is characterized by the presence of TP53 mutations.
Elevated rates of Wilms tumor are observed in patients with a number of genetic disorders, including WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome, Beckwith-Wiedemann syndrome, hemihypertrophy, Denys-Drash syndrome, and Perlman syndrome [8]. Other genetic causes that have been observed in familial Wilms tumor cases include germline mutations in REST and CTR9 [4, 14].
^aMHHT Ba ннновацнн^ар - 06m,ecrBO u ннновацнн - Society and innovations Special Issue - 7 (2021) / ISSN 2181-1415
The genomic and genetic characteristics of Wilms tumor are summarized below.
The WT1 gene is located on the short arm of chromosome 11 (11p13). WT1 is a transcription factor that is required for normal genitourinary development and is important for differentiation of the renal blastema [28]. WT1 mutations are observed in 10% to 20% of cases of sporadic Wilms tumor [20, 26, 28].
Germline WT1 point mutations produce genetic syndromes that are characterized by nephropathy, 46XY disorder of sex development, and varying risks of Wilms tumor. Studies evaluating genotype/phenotype correlations of WT1 mutations have shown that the risk of Wilms tumor is highest for truncating mutations (14 of 17 cases, 82%) and lower for missense mutations (27 of 67 cases, 42%). The risk is lowest for KTS splice site mutations (1 of 27 cases, 4%). Bilateral Wilms tumor was more common in cases with WT1-truncating mutations (9 of 14 cases) than in cases with WT1 missense mutations (3 of 27 cases) [1, 3].
A second Wilms tumor locus, WT2, maps to an imprinted region of chromosome 11p15.5; when it is a germline mutation, it causes Beckwith-Wiedemann syndrome. About 3% of children with Wilms tumor have germline epigenetic or genetic changes at the 11p15.5 growth regulatory locus without any clinical manifestations of overgrowth. Like children with Beckwith-Wiedemann syndrome, these children have an increased incidence of bilateral Wilms tumor or familial Wilms tumor [16].
Approximately one-fifth of patients with Beckwith-Wiedemann syndrome who develop Wilms tumor present with bilateral disease, and metachronous bilateral disease is also observed. [7, 10, 24]. The prevalence of Beckwith-Wiedemann syndrome is about 1% among children with Wilms tumor reported to the National Wilms Tumor Study (NWTS) [10, 25].
Approximately 80% of patients with Beckwith-Wiedemann syndrome have a molecular defect of the 11p15 domai [15]. Various molecular mechanisms underlying Beckwith-Wiedemann syndrome have been identified. Some of these abnormalities are genetic (germline mutations of the maternal allele of CDKN1C, paternal uniparental isodisomy of 11p15, or duplication of part of the 11p15 domain) but are more frequently epigenetic (loss of methylation of the maternal ICR2/KvDMR1 or gain of methylation of the maternalICR1) [5, 16].
Several candidate genes at the WT2 locus comprise the two independent imprinted domains IGF2/H19 and KIP2/LIT1 [5]. LOH, which exclusively affects the maternal chromosome, has the effect of upregulating paternally active genes and silencing maternally active ones. A loss or switch of the imprint for genes (change in methylation status) in this region has also been frequently observed and results in the same functional aberrations [5, 15, 16].
A relationship between epigenotype and phenotype has been shown in Beckwith-Wiedemann syndrome, with a different rate of cancer in Beckwith-Wiedemann syndrome according to the type of alteration of the 11p15 region [30].
The aim of our study is to improve modern diagnostic methods in the study of pathomorphological changes developing in the kidneys in children with nephroblastoma.
The main objectives of the study are to identify macroscopic and microscopic changes in renal tissues in nephroblastoma in children, to study changes in renal tissues that develop in nephroblastoma in children, using the immunohistochemical method, to substantiate the criterion of the relationship between pathomorphological and immunohistochemical changes during development nephroblastomas in children.
^aMHHT Ba ннновацнн^ар - 06m,ecrBO u ннновацнн - Society and innovations Special Issue - 7 (2021) / ISSN 2181-1415
When assessing the pathomorphological features of nephroblastoma, data on autopsies are given, as well as general characteristics of the research methods used. In this study, a retrospective analysis of extracts from case histories, data obtained during autopsy, copies of materials obtained during laboratory studies, the results of clinical and laboratory studies that were obtained during autopsy in the pathomorphology department of the Republican Specialized Scientific and Practical Medical Center of Oncology and radio logic from 2008 to 2021.
In our studies, based on the results of the study, we study the relationship of pathomorphological changes that develop in the kidneys with nephroblastoma in children and between death. A full-fledged and comparative analysis of the relationship between pathomorphological and immunohistochemical changes in renal tissues is carried out.
Diagnosis of Wilms' tumor. If, after an external examination of the child and in the medical history, the pediatrician has a suspicion of Wilms 'tumor, then the doctor issues a referral to the Children's Cancer Hospital on suspicion of Wilms' tumor, it is necessary to carry out various tests and studies: firstly, to confirm the diagnosis, and secondly, to find out the specific form of nephroblastoma and to find out how much the disease has already spread throughout the body.
Having received answers to these questions, one can begin to plan the optimal treatment tactics and give a prognosis. An important role (after external examination) for the diagnosis is played by such diagnostic methods based on images as ultrasound studies (ultrasound), magnetic resonance imaging (MRI) and computed tomography (CT). With their help, Wilms' tumor can be distinguished from other diseases (for example, from neuroblastoma, from lymphoma or from neuroblastomatosis) with a certainty of up to 95%.
Also, according to the images, you can accurately estimate the size of the tumor and the degree of its prevalence throughout the body. But the condition for the most accurate diagnosis is the high quality of the technique and the extensive experience of the doctor who performs diagnostics based on the images. This is especially important here. Because in Germany, microscopic (histological) confirmation of the diagnosis, that is, when a tumor sample is taken and then examined under a microscope, is usually done after the initial course of chemotherapy. Clarification of the diagnosis and search for metastases. Sometimes it happens that it is impossible to accurately distinguish Wilms' tumor from other diseases, for example, from neuroblastoma, using the images.
Then an additional examination is prescribed. For example, MIBG scintigraphy is done to distinguish nephroblastoma from neuroblastoma. Or, the body is looking for certain tumor markers that can be found if a child has neuroblastoma. With nephroblastoma, they are not in the body. Other studies should confirm or exclude metastases in the body. Therefore, in order to find metastases in the lungs, an x-ray or computed tomography of the chest is always prescribed.
Morphological diagnostics. As with all other malignant tumors, the diagnosis of nephroblastoma is based on a morphological conclusion. However, with regard to nephroblastoma, an exception is allowed from the rule of biopsy before starting chemoradiation therapy. During the biopsy, a violation of the integrity of the pseudocapsule occurs, and the tumor detritus enclosed in the pseudocapsule, which has a mushy character, is scattered along the abdominal cavity or along the needle, which increases the spread of the tumor, changes the clinical stage of the disease (automatically translates into stage 3) and worsens the prognosis of the disease.
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Special Issue - 7 (2021) / ISSN 2181-1415
Therefore, in patients> 6 months and <16 years, the diagnosis of nephroblastoma is established with conservative examination. This is facilitated by the presence of clear diagnostic signs of nephroblastoma, which reduce diagnostic errors to a minimum. The histological diagnosis is made after preoperative chemotherapy. Confirmation of the diagnosis in a reference laboratory is mandatory. At the same time, some foreign protocols suggest the initial removal of the kidney with the tumor or its biopsy, even with doubtful tumor resectability.
In accordance with the NWTS strategy, this approach avoids the error of conservative diagnostics and conducts a thorough revision of the abdominal organs, excluding or detecting metastatic lymph nodes and a tumor of the opposite kidney (according to NWTS, in 30% of cases of bilateral nephroblastoma, a tumor of the second kidney is not visualized by conservative diagnostic methods). Diagnosis of a primary tumor is based on the identification of typical signs of nephroblastoma and the exclusion of other diseases.
The range of differential diagnoses includes malformations of the kidney, hydronephrosis, neurogenic tumors and other tumors of the retroperitoneal space, liver tumors, hamartoma. Diagnosis of nephroblastoma and stage determination includes laboratory studies and instrumental ones. Laboratory tests include: a clinical blood test, a general urinalysis, a biochemical blood test, and a study of catecholamines in urine and blood serum (to exclude neuroblastoma) [13].
Thus, the review of the literature showed that the issue under study has not been sufficiently studied in the domestic and foreign literature. Nephroblastoma is one of the most serious diseases in children among oncopathology, which requires dynamic monitoring of hemodynamic parameters and timely prescription of both pharmacological and mechanical means of prophylaxis. Prevention of the development of Wilms' tumor is one of the important steps to increase the survival rate of children with nephroblastoma.
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