Molecular mechanisms of hemostasis impairment in oncology

Malignant neoplasms are characterized by the presence of the hemostasis system pathology, predisposing cancer patients to thrombohemorrhagic complications. The pathogenesis of cancer-associated coagulopathy is complex and involves a variety of mechanisms. Tumor cells have the ability to activate the host’s hemostasis system, and this phenomenon is controlled by the same oncogenes that are responsible for neoplastic transformation. In addition to predisposing factors to impaired hemostasis from the side of the disease, the anticancer drugs themselves carry risks of developing coagulation disorders. The pathophysiological basis of this kind of disorders caused by chemotherapy is associated with damage to the endothelium, imbalance of coagulation and anticoagulant proteins, platelet dysfunction and their deficiency. In this article, the authors set themselves the goal of generalizing and updating the current knowledge of the molecular mechanisms that cause thrombohemorrhagic risk in cancer.

Key genetic disorders in the pathogenesis of neuroblastoma

Neuroblastoma (NB) is a malignant neoplasm of the sympathetic nervous system of embryonic origin, consisting of undifferentiated neuroectodermal cells of the neural crest.In the structure of the incidence of malignant neoplasms in patients under one year of age, NB is the most common tumor. At the same time, mortality of this disease ranks third, behind leukemias and tumors of the central nervous system, and amounts to 13% in the structure of child mortalityfrom malignant tumors in developed countries. The stratification of patients to the risk groups and the subsequent determination of treatment tactics depends on several prognostic factors, including genetic aberrations identified in tumor cells. Moreover, processes such as spontaneous regression and transformation into benign tumors are due to the genetic characteristics of NB. Thus, the study of genetic disorders underlying the pathogenesis of NB is necessary for adequate subdivision of patients into risk groups and developing of new methods of treatment.

The role of platelets in tumor cell metastasis

Platelets are small, nuclear-free cells whose main function is to stop bleeding. In addition to performing a hemostatic function, platelets are also involved in immune and inflammatory processes. Extensive experimental data suggest that platelets support tumor metastasis and their activation plays a critical role in cancer progression. In the circulatory system, platelets protect tumor cells from immune elimination and promote their arrest at the endothelium, supporting the formation of secondary lesions. Due to the significant contribution of platelets to tumor cells survival and propagation, antithrombotic drugs are considered as a novel anti-metastasis approach. In this article, the authors set a goal to summarize and update the currently existing knowledge about the molecular mechanisms and the role of platelets-tumor cells interaction, as well as to discuss the possibility of platelets receptors as anti-metastasis targets.

Russian recombinant coagulation factors: the technological background and the results of clinical studies

The prolongation of survival and the improvement of quality of life in patients with hemophilia A and B are only possible if hemostatic disorders caused by coagulation factor VIII and IX deficiency are managed effectively. Recombinant coagulation factors are playing an ever-increasing role in the preventive care of affected patients. The development, production and use of domestic recombinant coagulation factors opened up new treatment opportunities and improved access to preventive care for hemophilia patients. The results of clinical studies on the efficacy and safety of the Russian recombinant factors showed that they had similar efficacy and safety compared to the plasma derived clotting factors.

Choroid plexus papilloma and atypical choroid plexus papilloma in children: treatment results

Choroid plexus tumors (CPTs) are rare intraventricular tumors, accounting 2–5% of brain tumors in children. Choroid plexus papilloma (CPP) classified by the World Health Organization (WHO) on the basis of histological criteria as benign tumor (WHO grade I), CPPs accounts for 10–20% of brain tumors during the first year of life, the median age of patients with CPP at the time of diagnosis – 3.5 years. Atypical choroid plexus papilloma (APP) is an intermediate (WHO grade II) tumor which was officially included in the WHO classification in 2007. Median age 0,63 years. In this work, for the first time in the Russian literature, we present the outcomes of CPP and APP therapy in a large cohort of patients. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. In our study from January 1, 2009 to December 31, 2019, 83 CPP and 37 APP were histologically verified. For all patients, surgical removal of the tumor was the first stage of treatment. In 79 (95.2%) patients with CPP and in 32 (86.5%) children with APP, radical resection was performed at the first stage. In 73.5% of children with CPP and 62.2% of children with APP there was no intra- and postoperative complications. In both CPP and APP, the 5-year EFS in patients with complete resection was statistically significantly higher compared to subtotal tumor resection (100% and 33 ± 27% in CPP, 94 ± 4% and 25 ± 22% for APP) (p < 0.001). Chemoradiation therapy was given to 1 patient with CPP, 4 patients with APP with tumor recurrence/progression.

Clinical variants of esophageal stenosis caused by infectious esophagitis in children

Infectious esophagitis (IE) is commonly seen in immunocompromised patients. IE may be the first symptom of immunodeficiency state, also can be complication of immunosuppressive therapy in patients with hematological and oncological diseases. Severe complication of IE is esophageal stenosis. Patient management tactics continue to be discussed. A purpose of our publication is to demonstrate our experience in the management of patients with infectious esophageal stenosis. The etiology, features of the clinical and endoscopic picture, as well as the effectiveness of drug therapy and endoscopic methods of treatment have been analyzed. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. In each case, parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications.

A case report of atypical malignant melanotic neuroectodermal tumor of infancy

Melanotic neuroectodermal tumor of infancy is a rare neoplasm that predominantly involves cranial bones and tends to occur during the first year of life. About 500 cases have been described in the literature to date; 6% of them have been reported to be malignant. Treatment for these malignant tumors was not documented and often turned out to be ineffective.Here we report a case of a child aged 2 years and 4 months who presented with a rapidly growing mass in the maxillary region spreading through the orbit into the anterior cranial fossa. The patient’s parents gave consent to the use of their child’s data, including photographs, for research purposes and in publications. He was treated at the Russian Children’s Clinical Hospital from July 2018 to November 2019. The child underwent chemoradiation and staged surgical removal of the tumor. Treatment with ICE and radiation therapy led to a significant reduction of the tumor volume and enabled us to perform cytoreductive surgery with the removal of the mass in the maxilla. Further treatment according to the CWS 2009 guidance for high-risk patients with NRSTS (NonRhabdomyosarcoma Soft Tissue Sarcoma) and radiation therapy resulted in further regression of intraorbital and intracranial components of the tumor and we performed a radical resection of the residual tumor conglomerate. Investigations during the course of treatment revealed no signs of metastatic involvement. The behavior of malignant melanotic neuroectodermal tumors of infancy is unpredictable, that is why in case of the massive involvement of the facial bones when surgery is associated with a high risk of functional impairment or cosmetic deformity, one should consider preoperative chemotherapy to reduce tumor size and intraoperative blood loss. Moreover, chemotherapy in combination with resection makes it possible to minimize the risk of local relapse or metastasis.

The prevalence of bloodborne infections (hepatitis B and C, human immunodeficiency virus) among pediatric patients with oncological and hematological diseases and immunodeficiencies

Patients with oncological and hematological diseases are at high risk of acquiring bloodborne infections due to multiple blood transfusions and frequent parenteral exposure. In order to evaluate the prevalence of bloodborne infections (i. e., hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)), we analyzed data on the seroprevalence of these viruses in patients admitted to the D. Rogachev NMRCPHOI from 2014 to 2020. We also performed a comparative analysis between these data and the prevalence of these infections in the total child population in Russia. The study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI. Among patients admitted to the D. Rogachev NMRCPHOI, the mean seroprevalence was 1.7% for hepatitis C, 0.2% for hepatitis B, and 0.1% for HIV. The seroprevalence of hepatitis B and C among our patients was 6 and 50 times higher than the prevalence among Russian children and adolescents, respectively. The prevalence of HIV among patients treated at the D. Rogachev NMRCPHOI was 3 times higher than that among the child and adolescent population in Russia. In patients with oncological and immunological diseases, the detection of HBV DNA, HCV RNA, and Anti-HBc is considered clinically useful and plays an important role in the diagnosis of occult hepatitis infections which cannot be identified with routine diagnostic tests. Our study with pediatric patients with oncological, hematological, and immunological diseases highlights the problem of nosocomial transmission of bloodborne pathogens. HCV transmission in medical facilities is the most pressing issue that requires the implementation of healthcare programs aimed at preventing parenteral transmission and at ensuring the safety of donated blood.

Giant cell angioblastoma

Giant cell angioblastoma is an extremely rare tumor of vascular origin, described at the end of the 20th century. It belongs to tumors with intermediate malignant potential and is characterized by locally infiltrative growth. The tumor doesn’t have any clear distinctive clinical characteristics. The diagnosis is established on the basis of histological examination. Two main treatment options for this pathology are discussed in the literature: radical removal of the tumor and therapy with low doses of interferon alpha. As a rule, this is a combination treatment. This article describes our own clinical case. The patient’s parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications. Interest is in the rarity of the disease and the features of the clinical characteristics of this case, specifically the extremely unfavorable localization in the oropharynx region and, accordingly, the impossibility of carrying out not only a radical removal of the tumor, but also its resection. The high probability of developing irreversible neurological complications in this age group associated with interferon alpha therapy questioned the possibility of its use. For the first time in this histological variant of a vascular tumor, chemotherapy was applied, including metronomic therapy with cyclophosphamide and vinblastine in combination with a liposomal form of doxorubicin. After 8 courses of chemotherapy, a complete clinical response was obtained with the restoration of the patency of the respiratory and digestive tracts. The observation period at the time writing of this article was 36 months.

The novel coronavirus disease (COVID-19) in children with cancer, hematologic malignancies, and severe immunodeficiencies. Results of monocenter study

Data on clinical manifestations of COVID-19 in immunocompromised patients in Russia is lacking, which prompted us to conduct a study to investigate clinical manifestations, risk factors, and outcomes of SARS-CoV-2 infection in children with oncological and hematological diseases treated at the D. Rogachev NMRCPHOI (Center). In this retrospective-prospective, nonrandomized, non-interventional study we enrolled children under 18 years with cancer, hematologic malignancies, and primary immunodeficiencies (PIDs) who underwent treatment at the Center from April 2020 to October 2021. COVID-19 cases were confirmed by polymerase chain reaction testing and classified as asymptomatic, mild, moderate, severe and critical. The study was approved by the Independent Ethics Committee and the Scientific Council of the Center. The study included 89 patients with a median age of 9.7 years and almost equal gender distribution (the male-to-female ratio was 1.1:1). Most patients (74%) were infected in a family claster. The main underlying diseases were: hemoblastoses (43.8%), solid tumors (33.7%), PIDs (14.6%). The most common clinical symptoms were fever (29%) and respiratory symptoms (47%). In 79% of cases, patients were asymptomatic or had mild symptoms; 21% of patients had moderate and severe disease (16% and 5%, accordingly). Risk factors associated with severe COVID-19 included lymphopenia (p < 0.001) and hematopoietic stem cell transplantation (HSCT) (p = 0.002). Full recovery was documented in 84% of the patients, 16% died, however COVID-attributed mortality was 5.5%. The highest mortality was in patients with moderate/severe COVID-19 (47% vs 7%, p < 0.001), in those with progression/ relapse of the underlying disease (36.3% vs 6%, p = 0.02), in children who had received specific therapy within a year before the SARS-CoV-2 diagnosis (21% vs 0%, p = 0.02), among HSCT recipients (31.6% vs 12.1%, p = 0.02), and patients with concomitant infections (33% vs 9.2%, p < 0.01). Factors associated with poor prognosis were moderate or severe COVID-19, relapse/ progression of the underlying disease, specific treatment (HSCT in particular) within 1 year before the SARS-CoV-2 diagnosis, concomitant infections, and lymphopenia. Data obtained in this study can help physicians with management decisions at this population of patients.