Treatment intensification in patients with intermediateand high-risk neuroblastoma (NB) has led to improved survival rates. However, NB survivors face a high risk of long-term side effects associated with intensified therapy, with second malignant neoplasms (SMN) being the most serious and occurring in 1.2% of cases. Our study included 176 cancer survivors who had been treated for intermediateand high-risk NB at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. Specific treatment was carried out according to the modified GPOH NB-2004 protocol from January 2012 to December 2019. High-dose preparative chemotherapy regimens included carboplatin/etoposide/melphalan (CEM) (until June 2013) and treosulfan/melphalan (TreoMel) (from July 2013). Starting from July 2014, high-risk NB patients with metabolically active residual tumors received 131I-metaiodobenzylguanidine (131I-MIBG) therapy after induction chemotherapy. Thirty-six (20%) patients enrolled in our study developed disease relapse. Treatment for relapsed NB depended on the initial risk group, the extent of previous therapy and the type of relapse. The median follow-up time from the date of diagnosis of NB to the date of last follow-up for the patients included in the study was 76 months (range 37–152 months). The final analysis was performed on 31 December 2023. All the patients diagnosed with a second malignancy underwent molecular genetic testing for germline and somatic gene variants at the Laboratory of Molecular Biology and the Laboratory of Molecular Oncology of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian Federation. High-throughput sequencing of DNA isolated from tumor tissues was used for the detection of somatic variants (Genetic Characteristics of Pediatric Solid Tumors panel (Pediatric Oncopanel v.4.2)) and whole-genome sequencing of DNA isolated from the patients’ peripheral blood was utilized for the detection of germline mutations in genes associated with tumor predisposition syndromes. Three (1.7%) out of 176 patients developed SMNs: papillary thyroid carcinoma (n = 2) and secondary acute myeloid leukemia (n = 1). At the diagnosis of NB, they had been aged 39, 52, and 55 months. Two of them had been initially stratified to the high-risk group, and one case had been allocated to the intermediate-risk group (and subsequently developed a combined relapse). The two patients from the high-risk group received high-dose chemotherapy as a part of frontline treatment, while the patient with intermediate-risk NB was given high-dose chemotherapy at the time of relapse. 131I-MIBG-therapy as a component of frontline therapy and cranial radiotherapy at relapse were performed in one case. The time from the date of NB diagnosis to the development of second malignancy was 66.5, 76.5, and 56.6 months. The cumulative incidence of SMN in the patients diagnosed with intermediateand high-risk NB after 5, 6, and 7 years was 0.73% (95% confidence interval (CI) 0.01–5.07), 1.64% (95% CI 0.41–6.44), and 2.75% (95% CI 0.88–8.42), respectively. Our molecular genetic analysis revealed the presence of somatic genetic variants in the tumor tissue samples, however, no germline mutations were found in the regions of interest. Second malignancies are rare but serious complications of NB treatment. It is important to closely follow-up surviving patients after treatment for NB, and a follow-up care program should be based on the extent of the prior treatment.

THE AIM OF THE STUDY:To develop and implement a comprehensive algorithm for the rehabilitation of patients after partial resection of the mandible using a titanium «growing» endoprosthesis. MATERIAL AND METHODS:The study included 16 patients aged 2 to 7 years, with benign (6 cases) and malignant (10 cases) tumors of the mandible. The patients were divided into 2 groups depending on the time of fixation of the endoprosthesis. Group 1 included patients with simultaneous installation of a prosthesis (7 people). Group 2 included patients with delayed installation of an endoprosthesis (9 people). For the reconstruction of the mandible, «growing» titanium endoprostheses made of Ti6Al4V alloy of various designs were used. Removable orthodontic devices of mechanical and functional type of action, standard elastic mouthguards were used in the process of dental treatment. RESULTS:A comprehensive algorithm has been developed for the rehabilitation of children after partial resection of the mandible, depending on the time of fixation of the prosthesis and the volume of surgical intervention. CONCLUSION:The developed algorithm of complex rehabilitation using a «growing» endoprosthesis and dental support at the pre and postoperative stages allows to reduce the volume of secondary deformation of facial structures and dentition.

We conducted a retrospective sample study with prospective collection of follow-up data. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. In the time period from January 2013 to August 2020 (92 months), 126 patients with head and neck soft-tissue sarcomas (STS) received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. We included 25 patients who had undergone surgery for neck STS and divided them into 4 groups (rhabdomyosarcoma (RMS), non-RMS-like STS, RMS-like STS, IRS-IV STS – with distant metastasis at baseline). The median age at the time of correct diagnosis was 2.6 (0.5; 5.0). The median time from symptom onset to the verification of the correct pathomorphological diagnosis was 3.2 (1.6; 4.9) months. We discovered a significant number (13/25, 52%) of cases of biopsy that was performed improperly (excessive/non-diagnostic biopsy, fine-needle aspiration biopsy) at a general inpatient facility. The correct pathomorphological diagnosis was clinically and statistically much more often made at a reference center (20/25, 80%; p = 0.003). Moreover, more than half of pathomorphological diagnoses (8/13, 62%) made at a general inpatient facility were later changed at a reference center. Radical resection was achieved in 17/20 (85%) survivors. In 3/20 (15%) cases, a repeat surgery was not needed because of the patients' complete response to protocol-based treatment. Radiotherapy was carried out in 11/25 (44%) cases. Protocol-based treatment was completed in 19/25 (76%) patients, 18/25 (72%) patients achieved complete response, 2/25 (8%) patients were considered incurable, and 4/25 (16%) children died before the completion of therapy. Post-operative complications of varying severity were observed in 10/25 (40%) cases and were dependent on the degree of STS extension and the severity of the condition of the patients undergoing intensive protocol-based treatment. The median time of patient observation since diagnosis verification was 33.2 (15.6; 74.2) months. The five-year overall survival (OS) was 76.3% (95% confidence interval (CI) 51.8; 89.5), the five-year event-free survival without local disease progression – 73.9% (95% CI 41.8–90.1). Even though there weren't many patients with IRS-IV in our study (4/25, 16%), their exclusion from the analysis resulted in a higher 5-year OS rate: 88.2% (95% CI 60.2; 96.9). This study revealed significant problems in the differential diagnosis of neck STSs in children. In most patients receiving optimal protocol-based treatment, neck tumors can be radically removed at a specialized healthcare facility without mutilating surgery, which results in high 5-year OS and event-free survival rates in patients without distant metastasis. Our findings require further investigation in a larger sample of patients.

Authors analyze bibliographical data on the treatment of osteosarcoma and Ewing's sarcoma of the maxillofacial region in children and adolescents. The role of surgical treatment in the primary lesion of this localization is analyzed in detail as well as the complex therapeutic approaches.

Primary hyperparathyroidism (or PHPT) is a rare pediatric disease occurring in 1 case per 200 to 300 thousand children. The most common cause of PHPT in the adult population is a solitary parathyroid (PT) adenoma with up to 16% of PT adenomas having an ectopic location. There are no epidemiological data on pancreatic adenomas in pediatric population including atypically located ones, and clinical data are extremely scarce. This article describes a clinical observation of an adolescent patient with PHPT whose disease has been manifested with increased fragility and deformation of the bones of the skeleton. Only one year after the onset of primary symptoms a complex set of diagnostic measures was initiated, as a result of which a diagnosis was established: PHPT against the background of adenoma of the pancreas, ectopic in the left lobe of the thymus. The surgical treatment was carried out in the amount of thoracoscopic hemithymectomy which led to the relief of hyperparathyroidism. Despite the surgical intervention the systemic osteoporosis and persistent pathological changes in the bone skeleton that have been formed by the time of diagnosis require long-term observation and treatment of the patient by a pediatric endocrinologist, pediatric orthopedist and rehabilitologist. Thus, based on the presented clinical observation, the conclusion is as follows: in order to minimize the risk of disability in children and adolescents with PHPT it is extremely important to establish the correct diagnosis as early as possible coupled with the timely etiotropic and pathogenetic treatment.

Germ cell tumors (GCT) are a heterogeneous group of neoplasms occurring predominantly in childhood and including several histological types characterized by different lesion localization and different clinical symptoms. Malignant GCT, such as yolk sac tumor (YST), in the head and neck region are extremely rare, therefore, only few clinical observations have been described in the literature. The aim of this study was to analyze the clinical data and treatment results of patients with yolk sac tumors of the head and neck region. Material and methods. During the period from 02.2012 to 02.2021 (108 months), 4 patients with YST of the head and neck area were treated at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. Median age at diagnosis was 22.2 months (range 6.9–36.2 months). Primary tumor was located in the orbit in 2 (50%) patients, in maxilla in 1 (25%) patient, and in nasal cavity in 1 (25%) case. Median alfa-fetoprotein (AFP) level before therapy was 4395 ng/ml (range 541–19453 ng/ml). The diagnosis was morphologically confirmed in all cases. Distant metastases in lungs were detected in 1 (25%) patient. The stage distribution was the following: II – 1 (25%), III – 2 (50%), IV – 1 (25%). Results. All the patients have received combined treatment according to the protocols of the German MAKEI group. Orbito-facial resections were required in 2 (50%) cases. By the time of the analysis, all patients are alive with no signs of recurrence and the median follow-up of 30.9 months (range 12.7–89.0). Conclusions. The main conclusion of this study is that the combined treatment, which is the standard of care, allows to achieve high overall survival rates, however, in some cases, complex anatomical localization of the tumor may require mutilation operations. Герминогенно-клеточные опухоли (ГКО) – гетерогенная группа новообразований, которая наблюдается преимущественно в детском возрасте, включает несколько гистологических типов, характеризуется раз- личной локализацией поражения и клинической симптоматикой. Злокачественные ГКО, такие как опухоль желточного мешка (ОЖМ), в области головы и шеи встречаются крайне редко, поэтому в литературе опи- сано мало клинических наблюдений. Целью настоящего исследования является изучение клинических данных и результатов терапии у пациентов c ОЖМ в области головы и шеи. Материал и методы. За период 02.2012–02.2021 гг. (108 месяцев) в ФГБУ НМИЦ ДГОИ им. Дмитрия Рогачева получали лечение 4 пациента с ОЖМ в области головы и шеи. Медиана возраста на момент постановки диагноза составила 22,2 месяца (разброс 6,9–36,2 месяца). Опухоль локализовалась в обла- сти орбиты у 2 (50%) пациентов, по 1 (25%) случаю пришлось на поражение верхней челюсти и полости носа. Медиана уровня α-фетопротеина до начала лечения – 4395 нг/мл (разброс 541–19453 нг/мл). Диагноз во всех случаях подтверждался результатами гистологического исследования. Отдаленные метастазы диагностированы у 1 (25%) пациента (легкие). Распределение по стадиям: II – 1 (25%), III – 2 (50%), IV – 1 (25%) пациент. Результаты. Всем пациентам проведено комбинированное лечение по протоколу MAKEI. У двух па- циентов потребовалось выполнение орбитофациальных резекций. На момент проведения настоящего анализа все пациенты живы без признаков заболевания, медиана длительности наблюдения составила 30,9 месяца (разброс 12,7–89,0). Выводы. Основным выводом настоящего исследование является то, что комбинированное лечение, яв- ляющееся стандартом терапии, позволяет добиться высоких показателей общей выживаемости, однако в ряде случаев сложная анатомическая локализация опухоли может требовать выполнения калечащих операций.

The aim of this article was to present a clinical case of juvenile ossifying fibroma in a child involving the maxilla, spreading into the maxillary sinus, nasal cavity, ethmoid sinus, and the orbit. The tumor was removed with simultaneous reconstruction of the maxillofacial defect using a vascularized fibular flap. The operation in the affected area was performed exclusively by intraoral access, which allowed to avoid face scarring. No tumor recurrence was detected during the 18 months of follow-up. Представленная статья освещает клинический случай ювенильной оссифицирующей фибромы у ребенка, поражающей тело и альвеолярный отросток верхней челюсти, с распространением в верхнечелюстную пазуху, правую половину полости носа, решетчатый лабиринт, орбиту. Проведено удаление опухоли с одномоментной реконструкцией дефекта челюстно-лицевой области с использованием реваскуляризированного малоберцового трансплантата. Операция проведена внутриротовым доступом, что позволило избежать появления рубцовых из- менений на лице. В период наблюдения, который составил 18 месяцев, данных за рецидив опухоли не обнаружено.

ПАПИЛЛЯРНЫЙ РАК ЩИТОВИДНОЙ ЖЕЛЕЗЫ У ПАЦИЕНТА С СЕМЕЙНЫМ АДЕНОМАТОЗНЫМ ПОЛИПОЗОМАвторы: А.В

THE PURPOSE:Of the study was to improve algorithms and methods of complex dental rehabilitation of children and adolescents with maxillofacial neoplasms.MATERIALS AND METHODS:Sixty-seven patients aged from 2 to 17 years (average age 10.43±4.56; 30 boys, 37 girls) underwent complex rehabilitation as a part of neoplasm treatment (40 benign, 27 malignant). Patients were divided into 3 groups: group 1 aged 2 to 7 years; group 2 aged 8 to 12 years; group 3 aged 13 to 17 years.RESULTS:Structural integrity of upper and lower jaws was reconstructed using vascularized bone flaps (27 cases), non-vascularized bone flaps (5 cases), titanium reconstructive plates (11 cases) or individual titanium endoprostheses of the temporomandibular joint (2 cases). Orthodontic, orthopedic and surgical dental treatment was performed at all stages of rehabilitation of patients and had its own characteristics depending on the group affiliation.CONCLUSION:Algorithms for dental rehabilitation of children and adolescents with maxillofacial neoplasms have been improved on the base of performed treatment.

Aim. To estimate the effectiveness of the developed design of perioperative examination of patients and surgery of children and adolescents with thyroid neoplasms. Materials and methods. The data of surgical treatment and perioperative control of 70 patients’ condition from 2012 to July 2017 were presented. The features of perioperative control included prevention of postoperative hypoparathrosis, use of ACR TI-RADS system to interpret the thyroid ultrasound findings as the first line diagnosis of a malignant neoplasm and intraoperative electrophysiological neuromonitoring of the laryngeal nerves. The follow-up was 1 to 56 months. The quality of life was estimated using a questionnaire. Results. The basic risk factors of an intraoperative injury to the recurrent laryngeal nerve, postoperative hypocalcemia and hypoparathyrosis were found during the study. The disease duration and aggressive course and a number of surgeries in a patient significantly decrease their life quality (p<0.05). Conclusions. Comparison of quality of life indicators before and after a surgery and popula tion indicators of healthy adolescents revealed the advantage of using the developed scheme of perioperative control of surgical treatment of thyroid neoplasms in children and adolescents.

Aim. To estimate the effectiveness of the developed design of perioperative examination of patients and surgery of children and adolescents with thyroid neoplasms.Materials and methods. The data of surgical treatment and perioperative control of 70 patients’ condition from 2012 to July 2017 were presented. The features of perioperative control included prevention of postoperative hypoparathrosis, use of ACR TI-RADS system to interpret the thyroid ultrasound findings as the first line diagnosis of a malignant neoplasm and intraoperative electrophysiological neuromonitoring of the laryngeal nerves. The follow-up was 1 to 56 months. The quality of life was estimated using a questionnaire.Results. The basic risk factors of an intraoperative injury to the recurrent laryngeal nerve, postoperative hypocalcemia and hypoparathyrosis were found during the study. The disease duration and aggressive course and a number of surgeries in a patient significantly decrease their life quality (p<0.05).Conclusions. Comparison of quality of life indicators before and after a surgery and popula tion indicators of healthy adolescents revealed the advantage of using the developed scheme of perioperative control of surgical treatment of thyroid neoplasms in children and adolescents.

From 2015 to 2017, 14 surgical intervention for benign and malignant tumors of mandibular and maxillary regions, soft tissues in the temporal areas and extra organ soft tissue tumors of the head have been performed in the Department of Oncology and Pediatric Surgery of Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (Moscow). Simultaneous or delayed reconstructions were performed with a bone-muscle flap taken from the crista iliaca, with a fibular flap or a soft tissue radial flap. In all cases, the anastomoses were well-fixed and the flaps viable. The paper presents a clinical case of a 6-year old girl with a central gigantic cell granuloma of the mandibular body. The tumor was resected with a simultaneous reconstruction with a free fibular flap based on stereolythographic resection templates. By the time this paper was written, the duration of the follow-up exceeded 1.5 years. There is no relapse, the free flap is well-fixed and functional, and the child is socially adapted. Based on the radical resection of the primary tumor, preserved innervations of the chin soft tissues, full facial mimics and rapid social adaptation of the child, as well as functional preservation of the jaw and the possibility of oral nutrition, together with the possibility of prosthodontics in the post-operative period, we consider this treatment approach to be optimal for this case. The use of free flaps was highly optimal in all other cases as well, due to their advantages, such as highly radical resection, good functional and esthetic results, rapid social adaptation of children. We believe that wider indications for reconstruction with free flaps are very promising in pediatric practice.

A retrospective analysis was made in 63 patients who undergone the examination and treatment in Dmitry Rogachev National Research Center between January 2012 and August 2017. In the retrospective series 36 (57.1%) patients who underwent neck dissection for thyroid cancer and 27 (42.9%) head and neck cancer patients of other primary site. All patients underwent organpreserving block neck dissection. We detected statistically significantly more frequent metastatic lesion of the lymph nodes (p < 0.01), with fewer complications (p < 0.05), long-term disease-free survival and better outcomes (p < 0.01). Thus, thyroid cancer can be isolated into a separate class in which precision lymphodissection is of particular importance as an independent method of therapy and preventive treatment of metastatic involvement of the neck lymph nodes in head and neck cancer. It is especially important in children. As for other head and neck tumors, neck dissection is a secondary method of combined therapy.

A retrospective analysis was made in 63 patients who undergone the examination and treatment in Dmitry Rogachev National Research Center between January 2012 and August 2017. In the retrospective series 36 (57.1%) patients who underwent neck dissection for thyroid cancer and 27 (42.9%) head and neck cancer patients of other primary site. All patients underwent organpreserving block neck dissection. We detected statistically significantly more frequent metastatic lesion of the lymph nodes (p < 0.01), with fewer complications (p < 0.05), long-term disease-free survival and better outcomes (p < 0.01). Thus, thyroid cancer can be isolated into a separate class in which precision lymphodissection is of particular importance as an independent method of therapy and preventive treatment of metastatic involvement of the neck lymph nodes in head and neck cancer. It is especially important in children. As for other head and neck tumors, neck dissection is a secondary method of combined therapy.

Multidisciplinary approach is widely used worldwide among the specialists of different specialties. Joint efforts of oncologist, hematologist, surgeon, radiologist, pathomorphologist, anesthesiologist, ICU-staff, recreation therapist and other specialists are aimed on treatment of patients with hematological and oncological diseases. This manuscript showed the view of physicians on place of surgery in this complex system. Progress of surgery with the help of endoscopic technique, intraoperational navigation, reconstructive and microscopic technique open the width range of possibilities in diagnosing and treatment of patients. Only harmonious work of all staff members from the moment of patient’s entering to clinic to the successful healing, work of clinical-scientific parties allows to reach good oncological and functional results, to prepare new methods and introduce it to the practical usage. This will allow the early social adaption of children and adolescents.

Multidisciplinary approach is widely used worldwide among the specialists of different specialties. Joint efforts of oncologist, hematologist, surgeon, radiologist, pathomorphologist, anesthesiologist, ICU-staff, recreation therapist and other specialists are aimed on treatment of patients with hematological and oncological diseases. This manuscript showed the view of physicians on place of surgery in this complex system. Progress of surgery with the help of endoscopic technique, intraoperational navigation, reconstructive and microscopic technique open the width range of possibilities in diagnosing and treatment of patients. Only harmonious work of all staff members from the moment of patient’s entering to clinic to the successful healing, work of clinical-scientific parties allows to reach good oncological and functional results, to prepare new methods and introduce it to the practical usage. This will allow the early social adaption of children and adolescents.