This publication focuses on skin toxicity and skin manifestations of a chronic graft versus host disease (chGVHD). The article provides analysis of contemporary literature on these pathologies, presents new approach to preventing its development and also introduces pathogenetically determined patterns of non-drug correction of skin manifestations.
Background. The study of oncological morbidity in children, as well as the characteristics of its structure and the analysis of temporal trends within the subject of the Russian Federation is aimed at improving the organization of medical care: increasing early diagnosis, reliability of static data, and optimizing patient routing. Objective. Our aim was to analyze the incidence and its structure in children (0–17 years old) who lived in the Arkhangelsk Region and the Nenets Autonomous District in 2007–2016. Methods. The analysis of the incidence of malignant neoplasms of the child population in the Arkhangelsk region and the Nenets Autonomous District was carried out. Results. During the study period, the diagnosis of cancer was first established in 329 (including 6 patients from other subjects of the Russian Federation children (boys — 177, girls — 146) at the age of 0–17 years, of which 260 children at the age of 0–14 years and 63 — at the age of 15–17 years. The average annual incidence of children over 10 years was 14.3: for the age group 0–14 years old — 13.8, for the age group 15–17 years old — 16.6. During the analyzed period, there were significant fluctuations in annual incidence rates (minimum — 9.8 in 2010; maximum — 16.8 in 2009). The average annual incidence in the age group 15–17 years (16.6) was 18% higher than in the age group 0–14 years (14). The morbidity structure was characterized by some predominance of solid tumors (51.7%) over hemoblastosis (48.3%), and in the group of 0–14 years this ratio was 54.6/45.4%, in the group of 15–17 years — 50, 9/49.1%. Conclusion. In the analyzed subjects in recent years there has been practically no increase in the incidence in children. The incidence in the age group 15–17 years is slightly higher than in the age group 0–14 years. Changes in the morbidity structure are noted, mainly due to a decrease in the proportion of lymphomas.
Background. «Graft-versus-host» disease (GVHD) is a major complication of allogeneic Hematopoietic Stem Cell Transplantation (HSCT), the main cause of non-relapse mortality. The actual problems of alternative donors HSCTs are GVHD prophylaxis and its distinction from «graft-versus-tumor» (GVT) effect. Objective. Assessment of incidence and severity of GVHD in children with very high-risk cancer after non-T-depleted haplo-HSCT; searching some correlation between controlled chronic GVHD (chGVHD) and GVT effect after HSCT, compare cyclosporine (CSA) and tacrolimus based GVHD prophylaxis. Methods. We provided the GVHD assessment in 74 recipients of haplo-HSCs from relatives since 2001 till 2018 in retrospective cohort study. Effect of chGVHD on the HSCT results was assessed in 23 patients with acute myeloid leukemia (AML) and 15 patients with solid tumors. We analyzed the incidence of severe acute and chronic GVHD in patients who received CSA or tacrolimus-based prophylaxis. Results. The incidence of severe aGHVD in our study was 15%, chGVHD — 12%. Switch CSA to tacrolimus resulted in reduction of severe aGVHD from 21% to 9% and full elimination of severe extensive chGVHD. Controlled chGVHD after haplo-HSCT was associated with relapse reduction from 48.7% to 30% and improvement of overall survival (OS) from 46.5% to 80.8% in patients with AML. We haven’t seen any clinically significant antitumor effect of graft in patients with solid tumors. Conclusion. In our study the incidence of severe GVHD corresponds to world data after HSCTs from alternative donors, it went down after switch from CSA to tacrolimus. We found some correlation between controlled chGVHD development and HSCT results improvement in patients with AML. The GVT effect of haplo-graft in solid tumors is almost absent.
Background. Advances in oncology and hematology-oncology are associated with the development of advanced treatment programs. The main role among them one belongs to chemotherapy. Therapy requires adequate venous access and the most optimal is a fully-implantable venous system (venous port) that meets all the requirements for long-term and intermittent administration of drugs. Objective. The aim of our study was to analyze the experience of using IVAPS in the treatment of children with cancer in a multidisciplinary hospital. Methods. A retrospective study of the implantation of 192 IVAPS in children in the Morozovskaya State Children’s Clinical Hospital for 12 years from 2004 to 2015 was conducted. The average age of patients at the time of implantation is 53 months — 4 years and 4 months. The ratio by gender was equal. IVAPS were implanted under X-ray control in a surgery room by puncture technique in the subclavian and / or jugular veins mainly in patients with solid tumors (175/192; 91,2%), and with hemoblastomas (17/192; 8,8%). Results. The average lifetime of the IVAPS is 24 months. Intraoperative complications and complications in the short term (up to 30 days from the moment of implantation) were noted in 44/192 (23%) cases, in the long term (more than 30 days) — in 34/192 (17.7%). All intraoperative complications were resolved during surgery. In the long-term period, infection of the IVAPS was detected in 12 (6.25%) cases: gram-positive flora in 7/12 (58.3%) cases, gram-negative flora in 5/12 (41.7%); in 17/192 (8.9%) — thrombosis of the IVAPS, in 2/192 (1%) — violation of the integrity of the port-system. IVAPS were removed in 78/192 (40.6%) cases: due to the end of treatment — 66/78 (84.6%), due to infection — 12/78 (15.4%). 45/191 (23.6%) patients died from progression of the underlying disease, 89/191 (46.6%) achieved remission, 32/191 (16.8%) continue treatment, 25/191 (13.1%) dropped out from under observation. Conclusion. Considering the intensification of treatment protocols, it is reasonable to recommend the use of IVAPS in the treatment of children with cancer.
Background. The social significance of pediatric oncology and attention to the problems of treating children, both representatives of the authorities and the community, a small number of primary patients detected annually, a shortage of pediatric oncologists and pediatric oncological beds explain problems in organizing medical care for this category of patients. This requires a search for new approaches to the organization of medical care, based on scientific calculations. Objective. Our aim was to improve the organization of medical care for children with cancer in the Russian Federation. Methods: The operative reports for 2017 of executive bodies in the sphere of health care 81/85 (95.3%) of the subjects of the Russian Federation were analyzed. Results. The number of children was 28 132 685 people. (0–17 years), the number of child oncology departments — 47, children›s oncological beds — 1925 (0.7 for 10,000), the average number of days of berth employment in the year — 315.3 days. In 30 (35.3%) subjects of the department of pediatric oncology are absent, in 12 (14.1%) — there are no children›s oncological beds. The number of physicians that provide medical care to children with cancer — 392, of which 259 (66%, 0.09 for 10 thousand) have a certificate, a pediatrician oncologist. In 12 (14.1%) subjects, there are no doctors-children oncologists, 6 (7%) did not provide these data. In 6 (7%) subjects there are no children›s oncological beds and doctors-children›s oncologists. The incidence of malignant tumors was 13.2 (100,000 thousand) prevalence — 91.3, death rate — 2.5, a one-year lethality — 6.5%. Actually revealed 8.3% of patients. 1385 (37.4%) of primary patients were sent to medical organizations of federal subordination, 61 (1.6%) primary patients left the territory of the Russian Federation. Conclusion. It is necessary to take measures aimed at modernizing the system of rendering medical care to children with cancer, namely: to increase the reliability of statistical data, to analyze the needs of subjects in the number of children’s oncological beds and pediatric oncologists, to introduce criteria for selecting patients for children’s oncological beds as part of medical organizations of various levels, to minimize the deficit of doctors and children’s oncologists, to systematically increase the number of children’s cancer beds simultaneously dividing existing in accordance with the needs of the population and the level of congestion, as well as ensure the routing of patients in accordance with a three-tier model.
Background. Retinoblastoma is the most common intraocular malignant tumor in children. Substantial advances have been made in field of local treatment, in particular, through the development of selective intraarterial chemotherapy (SIAC). Life-threatening cardio-respiratory disorders were reported during the course of SIAC at the moment of a.ophthalmica catheterization. Objective. Our aim was to improve the safety and effectiveness of anesthetic management in children with retinoblastoma. Methods. The retrospective study included patients (n=203) who underwent SIAC (517) under general anesthesia in 2013–2018. Results. Hemodynamic parameters in patients who underwent SIAC procedure for the first time (211) were analyzed, in 186 (88%) cases, smooth anesthesia was observed, the deviations of blood pressure and heart rate did not exceed 20% of the baseline values. In 25 (12%) cases, patients who underwent the first SIAC procedure developed bronchospasm with a decrease in respiratory volume of up to 30% from the initial values 10–20 seconds after catheterization of a.ophthalmica with microcatheter. When analyzing hemodynamic parameters in patients who underwent repeated SIAC procedures (2nd, 3rd sessions, etc.) (306), in 177 (58%) cases, a clinical picture of the trigemino-pulmonary reflex of varying severity manifested. Conclusion. Severe cardio-respiratory complications are often observed during SIAC in children with retinoblastoma. These reactions occur predominantly during the second or subsequent procedures and can be potentially life-threatening. All patients with retinoblastoma who undergo SIAC should be considered at high risk.
Introduction: Histiocytosis is a heterogeneous group of rare diseases of unknown etiology. LCH is characterized by an abnormal proliferation of histiocytes (activated dendric cells and macrophages). Langerhans cell histiocytosis (LCH) is the most common form of histiocytosis, it is a potentially fatal diseases. Early detection of LCH plays an important role in its prognosis and outcome. However, the role of advanced methods of nuclear medicine in diagnosis of LCH is still to be researched. We have long-term experience in observing pediatric patients with LCH. Taking into the account the difficulty of diagnostic task for bone scintigraphy in identifying lytic bone destruction, we stated the following objective of the study.Purpose: Retrospective and prospective analysis of bone scintigraphy examinations of treatment-naive pediatric patients with LCH and calculate the diagnostic efficacy of bone scintigraphy. Material and methods: We analyzed 60 examinations of treatment-naive pediatric patients with proven case of LCH (2014-2019). The scanning was performed using whole body mode, 3 hours after intravenous injection of bone-seeking radiopharmaceutical 99mTc-MDP on Symbia E, T2 (Siemens, Germany). The median age was 5.6 years.Results: During examination we visualized 88 lesions with pathological level of accumulation of radiopharmaceutical in 60 patients. 84 with high level of accumulation (>120 %); 3 with slightly increased level of accumulation (100–120 %) and 1 with lower than normal level of accumulation (<100 %). The median level of accumulation of radiopharmaceutical was 268 %. Max level of accumulation was 1422 % (patient with subtotal involvement of femoral bone). Min — 60 % (patient with lytic destruction in orbital bone). During X-Ray we found out 97 pathological focuses of bone lytic destruction. In 3 patients with polyostotic form we found extra focuses on scintigraphy, which were confirmed with following examination and X-Ray. 8 lesions were not found on scintigraphy in 8 patients.Сonclusions: We evaluated diagnostic accuracy of bone scintigraphy with 99mTc-MDP in treatment-naïve pediatric patients with proven case of LCH. Sensitivity, specificity, NPV and PPV — 91.6, 50.0, 11.1, 98.6 %, respectively.
Background. The variety of the clinical features of vascular tumors in the maxillofacial area limits the choice of method and is able to make difficulties in the treatment. The combined method of treatment proposed by the authors (vascular sclerotherapy with concurrent propranolol intake) demonstrates high efficacy, lack of invasiveness, shortening the rehabilitation period and less side effects. Objective. The aim of the study was to increase the effectiveness of conservative treatment of vascular tumors of the maxillofacial area in young children by combining the method of sclerotherapy and taking propronolol. Methods. In a cohort study, the results of treatment of 80 children aged 2 months to 2 years with vascular tumors of the maxillofacial region (ICD-10: D18.0) were evaluated. A comparison was made of the results in 2 groups of children who were treated with different methods: combined (n =40; main group; sclerotherapy and taking propranolol) and propranolol monotherapy (n =40; comparison group). Analysis of the data obtained in the main group and the comparison group led to the development of the criteria for evaluating the treatment results: good (regression of vascular tumors and the absence of a cosmetic defect), satisfactory (reduction of vascular tumors by 2/3 or more with maintaining cosmetic defect) and unsatisfactory (gross cosmetic defect) in terms of changes in the volume of tumor, the diameter of the supply vessels and the values of the linear velocity of blood flow according to ultrasound data. Results. Subjects treated by the combined treatment had a significant regression of vascular tumors in the maxillofacial area compared with the comparison group: reduction of the tumor volume, diameter of the supply vessels and linear blood flow velocity according ultrasound data reached zero after 6 months from the start of combined treatment — 6 months earlier than in the comparison group (p <0.001). Conclusion. According to the results of the study, the advantage of the author’s method over the traditional method was demonstrated, which resulted in a reduction in the duration of treatment, a decrease in the risk as well as in a degree of complications.
Background. Poor-risk neuroblastoma treatment is still a challenge because of high relapse rate. Combination of high dose chemotherapy (HDCT) with MIBG I131 radiotherapy is a relatively new strategy for consolidation regimens in some patients with neuroblastoma. Objective. The aim of the study was to assess the safety and efficacy of a complex consolidation in a treatment of high-risk neuroblastoma patients in a pilot clinical trial. Methods. In our cohort study we analyzed toxicity along with 2- and 4- years OS and EFS in a cohort of 12 patients who got a consolidation based on Treo/ Mel HDCT in combination with MIBG I131 as a part of high-risk neuroblastoma treatment protocol since 2014 till 2018. The study was conducted in the Pediatric Oncology and Hematology Scientific Research Institute of Blokhin’s National Medical Cancer Research Center (Moscow). The treatment with MIBG I131 was done in settings of isolated ward of Russian Scientific Center of Roentgenology and Radiology. Results. Maximum cumulative organ toxicity of grade 2 or less was seen in 92% of patients. There was no treatment-related mortality. OS for 2 and 4 years was 87,5% ± 11,7% (for both time points). EFS for 2 and 4 years – 61,4 ± 15,3% and 49,1 ± 16,4%, respectively. Conclusion. Consolidation regimen based on Treo/Mel with MIBG I131 is safe. As a part of treatment program, it provides 4-years EFS for about a half of patients with poor-risk neuroblastoma with active residual tumor at the moment of consolidation.
Background. Low-grade gliomas are the most common brain tumors in children. Gliomas have a favorable prognosis, but in some cases relapses or continued tumor growth occur. With relatively similar clinical and morphological characteristics of tumors, it is rather difficult to select a group of patients who may have progression. Objective. Our aim was to study the impact of certain clinical, histological and molecular characteristics of tumors on the progression/recurrence. Methods. A retrospective cohort study was carried out. Clinical data, histological features and molecular markers (overexpression of phosphorylated ERK1/2 (pERK1/2), mutation of B-Raf kinase (BRAF V600E), deletion of CDKN2A gene (delCDKN2A) were studied in 90 patients with low-grade pediatric gliomas, who were treated in the Center for Pediatric Oncology, Hematology and Immunology during 2010–2018. In gliomas with signs of anaplasia expression of gene of the X-linked alpha-thalassemia syndrome (ATRX), a trymethylated form of histone 3 (H3K27me), p53, and mutation of the dehydrogenase 1 isocitrate 1 gene (IDH1R132H) were also evaluated. Immunohistochemistry and the hybridization in situ (FISH) was performed to evaluate the molecular markers. Results. Statistical analysis confirmed the importance of such factors as non-radical tumor removal (p<0.0001), repeated treatment (p<0.0025), overexpression of pERK1/2 (p<0.0001), histological signs of anaplasia (p<0.0022), areas of diffuse growth (p<0.001), BRAF V600E (p<0.0001), delCDKN2A (p<0.0099). In tissue of gliomas with anaplasia overexpression of pERK1/2, mutation BRAF V600E, delCDKN2A and ATRX loss were more common. When conducting multivariate analysis, non-radical tumor removal and the presence of one of the molecular markers significantly influenced the prognosis (p<0.0001). Conclusion. The definition of molecular markers and the simultaneous assessment of the degree of tumor resection allows us to distinguish a group of patients with a high risk of tumor recurrence / progression.
The incidence of esthesioneuroblastoma in children under 15 years of age is 0.1 per 100.000 children. Distinctive histological features of this tumor are diffuse accumulation of neuron-specific enolase, synaptophysin, chromogranin, and variable expression of cytokeratins. Diagnosis of the tumor includes endoscopic examination of the nasal cavity and nasopharynx, magnetic resonance imaging (MRI) and computed tomography (CT) of the skull base, paranasal sinuses with intravenous contrast. PET-CT is advisable to use for the detection of regional and distant metastases, as well as for suspected relapse. In patients of adult age, a negative effect on the outcome of the disease was detected, the detection of metastases in the lymph nodes of the neck, the presence of tumor cells at the edges of tumor resection and a high degree of malignancy of the tumor according to the Hyams system. Therapeutic approaches depend on the stage of esthesioneuroblastoma by Kadish. In the A-stage, surgical treatment is advisable. In the presence of tumor cells at the edges of the resection or residual tumor, radiation therapy is performed. In case of B-stage, surgical treatment is combined with the mandatory irradiation of the primary tumor area. In patients with the C-stage, neoadjuvant chemotherapy or radiation is performed, followed by a surgical treatment, adjuvant chemotherapy and/or radiation therapy. Patients with D-stage chemoradiation therapy is indicated. There is no consensus on an effective drug regimen. Overall 5-year survival varies significantly depending on the design of the study — 55% to 98%. Further study of the features of the clinical picture, morphological and molecular features and the course of the disease will help to improve our understanding of the nature of the tumor.
Background. Lymphangiomas are non-specific malformations that develop from the lymphatic vessels. Usually, the disease is asymptomatic, but there may be complications requiring emergency care. In the literature there is no consensus about the method of choice in the treatment of these formations. Description of A Case Series. The article is devoted to the evaluation of the efficacy of surgical treatment of lymphangiomas in children. There are also several clinical cases showing mediastinal lymphangioma with a clinical picture of respiratory failure, lymphangioma of the abdominal cavity, imitating the symptoms of an acute abdomen and lymphangioma of a rare anatomical localization. The results of treatment of 48 children for the period from 2008 to 2017 were analyzed at «Morozov Children Municipal Clinical Hospital» (Moscow). The basis of treatment was the removal of education within healthy tissues. When the radical intervention was impossible in 5 (10.4%) children we used resection of the tumor with sparing coagulation of the surface of the formation. Infectious complications arose in 3 (6.3%), lymphorrhea — in 13 (27.1%) patients. Recurrences of lymphangiomas developed in 2 (4.2%) patients. In the case of lymphorrhea, expectant management and parenteral nutrition were used. The repeated operations were performed with recurrences. The catamnesis ranges from 6 months to 10 years. Conclusion. Radical removal of lymphangiomas of internal organs can be recommended to children of any age as an effective way to treat this disease.
Background.Currently, vascular access is one of the most important aspects in specific and accompanying treatment of cancer patients regardless of their age and sex. Partially implanted venous catheters previously described by Hickman were widely applied all over the world. The introduction of completely implanted venous port-systems revolutionized health care delivery and improved the quality of life in patients with oncological diseases. A fully implanted venous port consists of a silicone catheter which distal tip is connected to a port tank implanted subcutaneously. Such a design allows providing safe and multiple adequate vascular accesses regardless of the patient’s clinical state.Case Report.We present a clinical case of a 10-year-old patient diagnosed with medulloblastoma of the cerebellopontine angle and the left cerebellar hemisphere. The case described spontaneous detachment of an implanted venous port catheter and its migration to the venous heart in a patient who underwent chemotherapy by venous access provided through implantation of the venous port.Conclusion.Our clinical case demonstrated a rare and potentially extremely dangerous noninfectious complication associated with the use of venous port-systems. Implanted systems require washing 1–2 times per month with heparinized solutions or solutions containing taurolidine when they are not used. Periodic chest radiographs can reveal integrity alterations of the system. Any implanted system should be removed when it is not used, or it should be monitored on a regular basis.
ОБОСНОВАНИЕ Саркомы мягких тканей и костей составляют 12% всех злокачественных опухолей детского возраста, характеризуются быстрым прогрессированием, гематогенным и лимфогенным метастазированием. Несмотря на достижения последнего десятилетия в области химиолучевого лечения сарком у детей, прогноз при распространенных стадиях опухолевого процесса остается неблагоприятным, и пятилетняя общая выживаемость больных не превышает 25–30% [1, 2]. До сих пор остаются неизученными иммунологические факторы прогноза при солидных опухолях у детей. DOI: 10.15690/onco.v5i1.1864 О.П. Колбацкая, Т.В. Горбунова, Н.Н. Тупицын
Background. Atypical teratoid rhabdoid tumor (AT/RT) of the central nervous system (CNS) is an aggressive malignant tumor, mostly affecting children younger than 3 years old. AT/RT is characterized by the deletion and/or mutation of gene SMARCB1/INI1, located in the long arm 22q11, leading to a loss of the nuclear expression of protein INI1, which may be detected by immunohistochemical assay with the anti-INI1 antibody. These tumors are mostly located in the brain, and their incidence in the spinal cord is very rare, with just a few publications on their clinical observations.Description of a Clinical Case. A clinical example of AT/RT in a two-year patient with the tumor located in the thoracic and lumbar spinal cord is described. The patient underwent surgical treatment consisting in the tumor resection and also chemoradiotherapy. Evaluation showed complete response. By the moment this paper was written, the duration of event-free survival of this patient was 27 months.Conclusion. This paper reviews the earlier published cases of spinal cord AT/RT, in which the most common location of the tumor was the cervical portion of the spinal cord. The maximum overall survival was 18 months, and the average overall survival was 9 months. In our clinical example, we demonstrate a long-term complete response to the multimodal treatment for AT/RT.
Background.Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the gold standard in diagnosing the pathological nature of undetermined thyroid nodules. However, in some instances limitations and shortcomings arise, making it insufficient for determining a specific diagnosis.Objective.Our aim was to evaluate the effectiveness of ACR TI-RADS classification of neck ultrasound as a first-line diagnostic approach for thyroid neoplasms in pediatric patients.Methods.A retrospective analysis was made of FNA and US protocols in 70 patients who underwent the examination and treatment at Dmitry Rogachev National Research Center between January 2012 and August 2017. In the retrospective series 70% (49/70) of patients undergone FNA and 43% (30/70) of them undergone repeated FNA. All US protocols were interpreted according to ACR TI-RADS system by the two independent experts. The clinical judgment was assessed using the concordance test and the reliability of preoperative diagnostic methods was analized.Results.According to histologic examination protocols, benign nodules reported greater multimorbidity 29% (20/70), compared with thyroid cancer 17% (12/70), complicating FNA procedure. A statistically significant predictor of thyroid cancer with a tumor size ACR TI-RADS showed a significant advantage of ACR TI-RADS due to higher sensitivity (97.6 vs 60%), specificity (78.6 vs 53.8%), positive predictive value (87.2 vs 71.4%), and negative predictive value (95.7 vs 41.2%). Concordance on the interpreted US protocols according to ACR TI-RADS classification between two experts was high, excluding accidental coincidence.Conclusion.The data support the feasibility of US corresponding to the ACR TI-RADS classification as a first-line diagnostic approach for thyroid neoplasm reducing the number of unnecessary biopsies for thyroid nodules.
