Vol 18, No 4 (2019)

WNTMBaccounts for about 10% of all medulloblastomas and have a favorable outcome in patients under 16 years according international data. We analyzed clinical and molecular characteristics of 20 patients with WNTMBpatients. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The molecular group verification was performed by Nanostring gene expression profiling. The detection of CTNNB1 and TP53 gene mutations was carried out with Sanger sequencing. WNT Medulloblastoma are mainly classic (18/20 patients), non-metastatic (19/20 patients). Gross total resection was performed in 18 patients. Somatic CTNNB1 mutations were found in 17 patients, somatic TP53 were identified in 2 patients. 19/20 assessable patients are disease-free with a median follow-up of 23 months. One patient died from the progression of the disease. WNT MB patients have an overall favorable outcome, even for metastatic and TP53 positive tumors. The reduction in the intensity of therapy is indicated forWNTMB in case of reliable identification ofWNTMB.

High-risk neuroblastoma (NB) is characterized by unsatisfactory treatment results and low probability of long-term survival despite the multimodal therapeutic approach (chemotherapy, surgical treatment, radiation therapy, autologous hematopoietic stem cell transplantation, etc.). One of the prognostic factors in this cohort of patients is the response to induction therapy. The article presents the experience of the intensification of induction therapy in 12 patients with high-risk NB with a poor response (mixed response, stable disease) to standard induction therapy who received treatment at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, assessing its impact on the prognosis of the disease. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Patients received an additional two courses of chemotherapy with the inclusion of a type I topoisomerase inhibitor topotecan (TCE – topotecan, cyclophosphamide, etoposide). This regimen of intensification of therapy has demonstrated its feasibility. The main grade 3–4 toxicity was hematologic. An improvement in response was achieved in 5/12 (41.6%) patients. However, long-term results of therapy remained unsatisfactory. The 3-year EFS was 16.7% (95% CI 0.0–37.8), the 3-year OS was 50.0% (95% CI 21.7–78.3). Thus, the intensification of therapy in patients with high-risk NB with a poor response to standard induction therapy did not improve treatment outcomes.

High risk of life threatening complications is distinctive for surgery of tumors, which are in contact with large main vessels. Planning for the removal of the primary focus of neuroblastoma (NB), characterized by similar localization, includes determining the timing and method of the operation, the required resection volume, predicting complications, developing ways to prevent them and relieve them. The study was approved by the Independent Ethics Committee and Scientific Board of N.I. Pirogova of RussianNationalResearchMedicalUniversity. The results of complex treatment of 11 children with NB of thoracoabdominal localization, aged from 9 to 55 months, are present in the research. 7 (64%) of them were stratified into a high-risk group, 3 (27%) – intermediate, 1 (9%) – low, according to the criteria of the NB-2004 protocol. The results were analyzed depending on the features of the operation and the course of the early postoperative period. The number of variants of tumor syntropy which coincided image-defined risk factors, revealed by computed tomography with contrast enhancement, was in the range from 2 to 7 (median – 5). The median volume of the removed part of the tumor was 95% (range from 92 to 98%). Among intraoperative complications aortic wall (1 (9%) observation), superior mesenteric vein (1 (9%) observation), right renal vein (2 (18%) observations), left renal vein (2 (18%) observations), inferior vena cava (2 (18%) observations) injury should be noted, which were sutured without subsequently detected hemodynamic disturbances and organ function. Complications in the early postoperative period were: partial ileus (1 (9%) observation), renal artery thrombosis (1 (9%) observation), inferior vena cava thrombosis (1 (9%) observation), pancreatic necrosis (1 (9%) observation). They demanded reoperation in two children: nephrectomy in a child with renal artery thrombosis at the fourth posroparative day and performing of anastomosis between the pancreas and small intestine at the 74 posroparative day in a patient with pancreatic necrosis. Among patients in the intermediate and high-risk groups, the event-free two-year survival rate was 50%, the total two-year survival rate was 88%. The prognosis of the disease does not reliably correlate with the duration of the relief of postoperative complications (p = 0.53) and the resection volume (p = 0.46). Surgical intervention and postoperative observation in children with NB of thoracoabdominal localization should be carried out by a team that has experience of similar operations, owning vascular suture technique, with a preliminary assessment of the image-defined risk factors. The purpose of the operation should be a resection aimed at cytoreduction and elimination of the mass-effect, without striving to remove all areas of the tumor. 

Hepatoblastoma (HB) is the most common malignant liver tumor in children. The level of alpha-fetoprotein (AFP) is used for monitoring the response to antitumor therapy and for diagnosing relapses. The occurrence of HB relapses with normal AFP levels in patients who had elevated levels of this tumor marker at disease onset is considered to be an uncommon situation. The aim of this study was to describe cases in which AFP-negative hepatoblastoma relapses developed. The study participants included two HB patients who were initially stratified into high-risk and standard-risk groups and who received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and the Petrovsky National Research Center of Surgery inMoscow. At the moment of relapse acknowledgement these patients had normal AFP levels, which was confirmed by serial measurements. Immunohistochemistry (IHC) tests were performed on paired samples of the tumor at disease onset and at disease relapse respectively to evaluate AFP expression. The presented clinical cases demonstrate that normal AFP levels, when accompanied by suspicious clinical symptoms, do not allow to exclude an HB relapse. The possibility of relapse with a normal AFP level reinforces the importance of following the current plan of screening tests, which includes not only an evaluation of AFP levels, but also other tests such as a chest X-ray and an abdominal ultrasound. Parents gave their consent to use information about the child in the article.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematologic malignancy. Our view of the cellular origins of this kind of tumor has been changing dramatically with the emergence of new data on the molecular biological and immunological characteristics of the tumor. This article discusses the clinical features of BPDCN, as well as the cytological, morphological-immunological and molecular genetic criteria for BPDCN diagnosis. Taking into account the rare incidence of BPDCN, as well as its rather complex diagnostic procedure, which requires an extended diagnostic antibody panel, standard methods of therapy have not been developed. Chemotherapy protocols for acute lymphoblastic leukemia and acute myeloid leukemia are used, with/without subsequent autologous/allogeneic bone marrow transplantation, but the results remain unsatisfactory. For the first time in Russian cancer research, this article provides a description of BPDCN in a 14-year-old child. A detailed clinical analysis of this rare tumor is provided, as well as dermatoscopy results and a description of the histological, immunological and molecular features of BPDCN, from the point of view of differential diagnosis. Parents patients agreed to use personal data in research and publications.

Chronic granulomatous disease is a primary immunodeficiency, characterized by a violation of the oxygen-dependent mechanisms of phagocytosis. Mutations in the genes encoding proteins of the NADPH-oxidase complex lead to a violation of the respiratory burst. Clinical manifestations are recurrent bacterial and fungal infections, and the development of granulomatous complications due to a defect in autophagy, accompanied by an increase in the level of interleukin-1 inthe blood. The treatment of this disease is continuous preventive antimicrobial therapy, and specific therapy for the treatment of granulomatous complications. Hematopoietic stem cell transplantation from an allogeneic or unrelated donor is currently considered to be only radical treatment for CGD. This article presents a clinical case of the manifestation of an X-linked form of chronic granulomatous disease with granulomatous manifestations in the absence of an infectious history. Parents patient agreed to use personal data in research and publications.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is treatment of choice for determined group of adult patients. Cytoreduction and HIPEC is usually used in patients with ovarian, gastric and colorectal cancer, appednix cancer, peritoneal mesothelioma and in some tumors of another localization. The experience of cytoreductive surgery and HIPEC  in childhood is limited due to the lower frequency of peritoneal carcinomatosis in pediatric population. However, about 30% of malignant tumors in children develop in peritoneal cavity and pelvis. High recurrence rate are typical for these tumors, particularly due to tumor rupture. Taking into consideration low frequency of epithelioid tumors in children HIPEC is used for patients with other tumor types such as desmoplastic small round cell tumor (DSRCT), germ cell tumors, rhabdomyosarcoma and others. The aim o this paper is the review of the literature and present experience analysis of cytoreductive surgery and HIPEC in children.

The blood coagulation system plays an important role in health and disease. It is a complex network of proteolytic reactions that is activated during injuries and controls the formation of a fibrin clot. Although new components and reactions have not been discovered for thirty years, during this time there has been a revolution in understanding of how this system works and what enzymes are the optimal targets for the therapy. At the same time, new methods of drug development, first of all, computer docking, which are ideally suited for the discovery of inhibitors of blood clotting enzymes, have appeared. In this review, an attempt has been made to correlate the lines of development of new ideas about the mechanisms of coagulation, new methods of searching for drugs and their combination, thanks to which now there are more and more potentially interesting molecules that can change the face of the anticoagulant therapy in the near future. In the review, molecular modeling methods, primarily docking, which are increasingly used at the initial stage of developing new drugs, the role of docking at the initial stage of developing new inhibitors are briefly considered and the structure of the active centers of factors Xa and XIa, which determines their interaction with inhibitors, are discussed in detail.