Choriocarcinoma in neonates and infants: A severe but curable disease.

Choriocarcinoma in neonates and infants (N-CC) is an extremely rare, but aggressive cancer, frequently observed with concomitant maternal disease. A retrospective, bi-national study of patients treated in France and Poland for infantile choriocarcinoma analysed eight cases of N-CC, median age of 6 weeks. All tumours were diffuse. Six patients received a platinum-based regimen, and five had delayed surgery on residual distant tumour sites. At the end of follow-up, four patients were in complete remission and four had died of the disease. In all but two cases, mothers had simultaneous metastatic choriocarcinoma. Even if the outcome remains poor, patients could be cured with multimodal therapy.

Use of salusin ß for predicting atherosclerosis and components of the metabolic syndrome.

Salusin ß is a bioactive peptide, detectable in many tissues and body fluids, first identified nearly 20 years ago. Since then, many studies have been performed to define the role of salusin ß, concentrating on its role in atherosclerosis and conditions leading to vascular injury such as hypertension, diabetes and hyperlipidemia, in which salusin ß seems to play a proatherogenic role. Previous literature has evaluated salusin as a predictor of atherosclerosis. Herein, we performed online research using 5 databases, namely PubMed, Ovid, Web of Science, Scopus, and Cochrane Library. Inclusion criteria were articles published in the years 2017-2022, concerning the association between salusin ß and obesity, atherosclerosis, hypertension, and hyperglycemia. The aim of the review was to provide comprehensive data regarding the latest studies in this area. The latest research confirms that salusin ß plays an important role in the development of vascular remodeling, inflammation, hypertension, and atherosclerosis. Additionally, the peptide is associated with hyperglycemia and lipid disorders, and its widespread activity makes it a potential therapeutic target. However, there is a need for additional studies to confirm the potential role of salusin ß as a novel target for treatment. Many of the reports were performed in animal models, while research conducted in humans was generally based on small groups of patients and not always compared with healthy controls; studies enrolling children are rare.

Laparoscopic nephron-sparing surgery and laparoscopic nephrectomy for Wilms' tumor.

Introduction: The place of laparoscopy in the resection of Wilms' tumors has remained debatable, but evidence that neoadjuvant chemotherapy causes tumor shrinkage has made laparoscopic nephrectomy (LN) a feasible option. Laparoscopic nephron-sparing surgery (NSS) is technically very demanding and seems to be feasible and effective only when performed by a very experienced surgeon. Aim: We report 7 cases of laparoscopic nephrectomy and 1 case of laparoscopic heminephrectomy for Wilms' tumor. Material and methods: Forty-two consecutive children with primary renal tumor underwent nephrectomy between 2013 and 2020; 11 had an LN. Among them there were 8 children with Wilms' tumor, with age between 13 months and 7 years. All patients received neoadjuvant chemotherapy according to the current SIOP protocol. The mean tumor volume before and after chemotherapy was 174.4 ml (range: 14.7-501) and 32.8 ml (range: 4.3-68) respectively. Results: Seven laparoscopic nephrectomies and one heminephrectomy were performed. No patient had an intraoperative tumor rupture. All children had an attempt of lymph node sampling (their number per pathology assessment was in the range 0-5). There were no intraoperative events. One complication after heminephrectomy occurred, which was urine leak. Five patients had stage I tumor and 3 had stage II. Seven patients had an intermediate-risk and one had a high-risk tumor. There were no local or distant relapses. All patients remained disease-free at a median follow-up of 71 months (range: 16-94). Conclusions: This report demonstrates the feasibility of LN in children with Wilms' tumors. The patients should be carefully selected and specific training in laparoscopy is necessary, particularly with regard to laparoscopic heminephrectomy.

Assessment of Metabolic Syndrome and Kidney and Heart Function in Childhood Cancer Survivors.

BACKGROUND: The survivors of childhood cancer suffer from a number of long-term side effects. These include atherosclerosis and cardiovascular diseases (CVDs) that develop earlier in adulthood than in the rest of the population. The aim of this study was to identify prognostic factors of developing atherosclerosis before the development of symptomatic CVD. METHODS: A total of 141 children that were 7-18 years old were examined; there were 116 survivors of childhood malignancies (hematopoietic and lymphoproliferative malignancies-52; neuroblastoma-22; Wilms tumor-24; other solid tumors-18) and 25 healthy controls. Anthropometric measurements, blood pressure measurements, ultrasonography of the abdomen, echocardiography, and laboratory tests were performed. RESULTS: There were no significant differences in gender distribution, time from the end of the treatment, weight, BMI, prevalence of central obesity, blood pressure and resistive index of the renal arteries, lipid profile, or glucose and fibrinogen levels. Patients with solid tumors had a significantly lower height and worse renal function. Patients with hematological malignancies significantly presented the lowest shortening fraction of the left ventricle. The salusin ß levels were significantly higher in the control group than among the patients. CONCLUSIONS: The type and severity of side effects are closely related to the type of neoplasm and the treatment that has been undergone. Careful observation and regular follow-up are necessary.

Segmental chromosomal aberrations as the poor prognostic factor in children over 18 months with stage 3 neuroblastoma without MYCN amplification.

Introduction: Patients with stage 3 neuroblastoma (NBL) according to International Neuroblastoma Staging System (INSS) without MYCN amplification represent a heterogenous group with respect to disease presentation and prognosis. Methods: Retrospective analysis of 40 stage 3 patients with NBL without MYCN amplification was performed. The prognostic value of age at diagnosis (under 18 vs over 18 months), International Neuroblastoma Pathology Classification (INPC) diagnostic category and presence of segmental or numerical chromosomes aberrations were evaluated, as well as biochemical markers. Array comparative genomic hybridization (aCGH) for analyzing copy number variations and Sanger sequencing for ALK point mutations were done. Results: In 12 patients (two patients under 18 months), segmental chromosomal aberrations (SCA) were found and numerical chromosomal aberrations (NCA) were found in 16 patients (14 patients under 18 months). In children over 18 months SCA were more common (p=0.0001). Unfavorable pathology was significantly correlated with SCA genomic profile (p=0.04) and age over 18 months (p=0.008). No therapy failures occurred in children with NCA profile over or under 18 months or in children under 18 months, irrespective of pathology and CGH results. Three treatment failures occurred in the SCA group, in one patient CGH profile was not available. For the whole group at 3, 5 and 10-year OS and DFS were 0.95 (95% CI 0.81-0.99), 0.91 (95% CI 0.77-0.97) and 0.91 (95% CI 0.77-0.97), and 0.95 (95% CI 0.90-0.99), 0.92 (95% CI 0.85-0.98) and 0.86 (95% CI 0.78-0.97), respectively. DFS was significantly lower in the SCA group than in the NCA group (3-years, 5-years, and 10-years DFS 0.92 (95% CI 0.53-0.95), 0.80 (95% CI 0.40-0.95) and 0.60 (95% CI 0.16-0.87) vs 1.0, 1.0 and 1.0, respectively, p=0.005). Conclusions: The risk of treatment failure was higher in patients with SCA profile, but only in patients over 18 months. All relapses occurred in children having obtained the complete remission, with no previous radiotherapy. In patients over 18 months, SCA profile should be taken into consideration for therapy stratification as it increases the risk of relapse and this group may require more intensive treatment.

Parenchyma Sparing Anatomic Liver Resections (Bi- and Uni-Segmentectomies) for Liver Tumours in Children-A Single-Centre Experience.

Purpose: To present a single-centre experience in bi- and uni-segmentectomies for primary liver tumours in children. METHODS: This study included 23 patients that underwent (bi)segmentectomy. There were 15 malignant tumours (hepatoblastoma-13 patients), 7 benign tumours, and 1 calcifying nested stromal epithelial tumour. RESULTS: The median tumour diameter was 52 mm (range 15-170 mm). Bisegmentectomy 2-3 was most frequently performed (seven patients), followed by bisegmentectomy 5-6 (four patients). The median operative time was 225 min (range 95-643 min). Intraoperative complications occurred in two patients-small bowel perforation in one and an injury of the small peripheral bile duct resulting in biloma in the other. The median resection margin in patients with hepatoblastoma was 3 mm (range 1-15 mm). Microscopically negative margin status was achieved in 12 out of 13 patients. There were two recurrences. After a median follow-up time of 38 months (range 12-144 months), all 13 patients with HB were alive with no evidence of disease. Two relapsed patients were alive with no evidence of disease. CONCLUSIONS: From the available literature and data presented here, we propose that (bi)segmentectomy can become a viable surgical option in carefully selected paediatric patients and is sufficient to achieve a cure. Further studies evaluating the impact of parenchymal preservation surgery on surgical and oncological outcome should be conducted with a larger dataset.

Asymmetric and Symmetric Dimethylarginines as Renal Function Parameters in Paediatric Kidney Diseases: A Literature Review from 2003 to 2022.

Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), inhibitors of nitric oxide synthase, play important roles in many processes in the body. Most data in the literature concern their importance in adult chronic kidney disease (CKD). According to them, SDMA well reflects the glomerular filtration rate (GFR), and higher ADMA concentrations are associated with hypertension and higher mortality. In addition, both substances are recognised cardiovascular risk factors in CKD. The purpose of this review was to summarise the studies on dimethylarginines in renal diseases in children, about which we have much fewer data. The review focuses specifically on dimethylarginine's relation to routinely used renal function parameters. Finally, we analysed 21 of the 55 articles published between 2003 and 2022 on dimethylarginines in kidney diseases in children (from birth to 18 years of age), obtained by searching PubMed/MEDLINE (search terms: "dimethylarginine" and "kidney").

Late effects of childhood cancer treatment in long-term survivors diagnosed before the age of 3 years - A multicenter, nationwide study.

BACKGROUND: The effect of age on the incidence of late sequelae that occur after anticancer treatment in childhood is still not fully elucidated. In this multicenter study of long-term survivors diagnosed before age of three, we investigated the prevalence of late effects many years after treatment. METHODS: The study group (n = 561) was selected from the Polish National Childhood Cancer Survivors Registry (n = 1761) created in 2007. A survivor was defined as an individual who has survived at least 5 years after completion of anticancer treatment. All children were diagnosed between 1991 and 2016, mean age at diagnosis was 1.82 years (range 0.03-2.99) and median follow up time - 9.85 years (range 5.0-23.6). They were treated in accordance with international protocols approved by the Polish Pediatric Leukemia and Lymphoma Group and Polish Solid Tumor Group. Chemotherapy alone was used in 192 (34.2%), chemotherapy and radiotherapy - 56 (10%), chemotherapy and surgery - 176 (31.4%), chemotherapy, radiotherapy, and surgery - 79 (14.1%), and surgery alone in 58 patients (10.3%). RESULTS: Of all patients enrolled to the study, only 94 (16.8%) had normal function of all organs. Seventy-six (13.5%) children developed dysfunction in one organ, another 83 (14.8%) had symptoms or complaints suggestive of dysfunction in two organs or systems, 88 (15.7%) had abnormalities in three organs, and 220 (39.2%) had at least four or more dysfunctions. In the entire study group, dysfunctions most frequently (> 20% of cases) involved the following organs/systems: circulatory - 21.8%, urinary - 30.8%, gastrointestinal - 20.8%, immune - 23.5%, vision - 20.7%, hearing - 21.8%, and oral and masticatory dysfunction - 26.9%. We did not find any significant differences in organ dysfunction between children diagnosed under the age of 1 and those diagnosed at the age of 1-3, except for a lower incidence of thyroid abnormalities (p = 0.007) and the higher prevalence of liver dysfunction in youngest patients. In the subset with longer follow-up period (> 10 years) more frequent thyroid abnormalities (p = 0.019), male (p = 0.002) and female (p = 0.026) gonads dysfunction, as well as musculoskeletal problems (p < 0.001) were observed. Among subjects who received radiotherapy compared to those who did not, short stature (p = 0.001), and dysfunction of the following systems/organs - circulatory (p = 0.049), urinary (p = 0.012), thyroid gland (p < 0.0001), nervous (p = 0.007), immunological (p = 0.002), liver (p = 0.03), dental or chewing difficulties (p = 0.001), hearing (p = 0.001) and musculoskeletal (p = 0.026) were more frequently reported. When multimodal therapy was applied (chemotherapy, radiotherapy, and surgery) a higher incidence of short stature (p = 0.007), urinary system disorders (p < 0.0001), thyroid dysfunction (p < 0.0001), hearing loss (p < 0.0001), and skin problems (p = 0.031) were observed. CONCLUSION: This study confirms that radiotherapy and some specific toxicity of cytostatics are the most important factors affecting organ function. Apart from a higher incidence of liver dysfunction in the youngest patients, there were no significant differences in organ and system toxicities between children diagnosed under the age of 1 and those diagnosed at the age of 1-3. We have shown that this group requires systematic, careful and long-term follow-up.

Isolated central nervous system relapses in patients with high-risk neuroblastoma -clinical presentation and prognosis: experience of the Polish Paediatric Solid Tumours Study Group.

Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier.

Contrast-enhanced ultrasound of adrenal hemorrhage: a helpful problem solving tool.

AIMS: A focal lesion in the region of the adrenal gland in a newborn often requires further assessment. Ultrasound (US) is the initial imaging method of choice in young children as it does not use radiation or require sedation and it has excellent spatial resolution. In this case series, we present contrast-enhanced ultrasound (CEUS) as a problem-solving tool in the evaluation of neonatal adrenal lesions. MATERIAL AND METHODS: The imaging and medical records of five patients with adrenal lesions were retrospectively reviewed. All patients underwent US as an initial examination and all had US follow-up. Additionally, two patients had MRI examinations. CEUS was performed in all patients as a follow up examination. The enhancement characteristics of the adrenal masses on CEUS were analyzed with the use of VueBox software. In addition, qualitative analysis of the cine loops for the presence of vascularization within the lesions was performed by consensus between two radiologists. RESULTS: The presence of an adrenal hematoma was correctly detected and characterized by CEUS in all five cases using VueBox perfusion analysis. Adrenal hematomas had no internal perfusion and flat time intensity curves. CONCLUSION: The quantitative and qualitative CEUS assessment of the mass can distinguish hemorrhage from a malignant lesion. Based on our findings, CEUS could serve as an alternative diagnostic tool to magnetic resonance imaging in the diagnosis of slowly resolving NAH lesions.

Diagnostic, Prognostic and Predictive Markers in Pediatric Germ Cell Tumors-Past, Present and Future.

Germ cell tumors (GCTs) are a heterogenous group of neoplasms in children and young adults, in which serum tumor markers have been demonstrated to be highly sensitive diagnostic and monitoring tools. The known "old" serum biomarkers, alpha-fetoprotein (AFP), human choriogonadotropin (ß-hCG) and lactate dehydrogenase (LDH), have some limitations in sensitivity and specificity. MIRNAs from the miR-371~373 (chromosomal locus 19q13.41) and miR-302/367 (4q25) clusters are universally over-expressed in malignant GCT tissue samples. The levels of miRNAs from these clusters are elevated in the serum. They seem to be highly sensitive and specific in malignant GCTs diagnosis and disease assessment during treatment and follow-up. The aim of our review was to present the role of serum tumor markers in the clinical staging, treatment monitoring and follow-up of pediatric patients with GCTs and show new possibilities. The serum levels of miRNAs seem to be a new, promising essential tool in the clinical management of GCTs.

Dimethylarginines in Children after Anti-Neoplastic Treatment.

Background and Objectives: According to a recent Cochrane systematic review, renal impairment can develop in 0-84% of childhood cancer survivors in the future. The renal function impairment in this patient group can be related to nephrectomy, nephrotoxic agents therapy, abdominal radiotherapy, and combinations of these treatment methods. In this study, in a population of patients after anti-neoplastic therapy, with particular emphasis on patients after Wilms' tumour treatment, we compared new substances which play role in the chronic kidney disease (CKD) pathogenesis (asymmetric dimethylarginine-ADMA, symmetric dimethylarginine-SDMA) with standard renal function markers (e.g., creatinine and cystatin C in serum, creatinine in urine, etc.) to assess the usefulness of the former. Materials and Methods: Eighty-four children, without CKD, bilateral kidney tumours, congenital kidney defects, or urinary tract infections, with a minimum time of 1 year after ending anti-neoplastic treatment, aged between 17 and 215 months, were divided into three groups: group 1-patients after nephroblastoma treatment (n = 21), group 2-after other solid tumours treatment (n = 44), and group 3-after lymphoproliferative neoplasms treatment (n = 19). The patients' medical histories were taken and physical examinations were performed. Concentrations of blood urea nitrogen (BUN), creatinine, cystatin C, C-reactive protein (CRP), ADMA, and SDMA in blood and albumin in urine were measured, and a general urine analysis was performed. The SDMA/ADMA ratio, albumin-creatine ratio, and estimated glomerular filtration rate (eGFR) were calculated. eGFR was estimated by three equations recommended to the paediatric population by the KDIGO from 2012: the Schwartz equation (eGFR1), equation with creatinine and urea nitrogen (eGFR2), and equation with cystatin C (eGFR3). Results: Both the eGFR1 and eGFR2 values were significantly lower in group 1 than in group 3 (eGFR1: 93.3 (83.1-102.3) vs. 116.5 (96.8-126.9) mL/min/1.73 m2, p = 0.02; eGFR2: 82.7 (±14.4) vs. 94.4 (±11.9) mL/min/1.73 m2, p = 0.02). Additionally, there were weak positive correlations between SDMA and creatinine (p < 0.05, r = 0.24), and cystatin C (p < 0.05, r = 0.32) and weak negative correlations between SDMA and eGFR1 (p < 0.05, r = -0.25), eGFR2 (p < 0.05, r = -0.24), and eGFR3 (p < 0.05, r = -0.32). Conclusions: The usefulness of ADMA and SDMA in the diagnosis of renal functional impairment should be assessed in further studies. eGFR, calculated according to equations recommended for children, should be used in routine paediatric practice.

Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors.

BACKGROUND: Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved to treat adult and pediatric patients with TRK fusion-positive cancer. The aim of this study was to evaluate the efficacy and safety of larotrectinib in patients with TRK fusion-positive primary central nervous system (CNS) tumors. METHODS: Patients with TRK fusion-positive primary CNS tumors from two clinical trials (NCT02637687, NCT02576431) were identified. The primary endpoint was investigator-assessed objective response rate (ORR). RESULTS: As of July 2020, 33 patients with TRK fusion-positive CNS tumors were identified (median age: 8.9 years; range: 1.3-79.0). The most common histologies were high-grade glioma (HGG; n = 19) and low-grade glioma (LGG; n = 8). ORR was 30% (95% confidence interval [CI]: 16-49) for all patients. The 24-week disease control rate was 73% (95% CI: 54-87). Twenty-three of 28 patients (82%) with measurable disease had tumor shrinkage. The 12-month rates for duration of response, progression-free survival, and overall survival were 75% (95% CI: 45-100), 56% (95% CI: 38-74), and 85% (95% CI: 71-99), respectively. Median time to response was 1.9 months (range 1.0-3.8 months). Duration of treatment ranged from 1.2-31.3+ months. Treatment-related adverse events were reported for 20 patients, with grade 3-4 in 3 patients. No new safety signals were identified. CONCLUSIONS: In patients with TRK fusion-positive CNS tumors, larotrectinib demonstrated rapid and durable responses, high disease control rate, and a favorable safety profile.

Factors affecting the prevalence of overweight and obesity in children with Down Syndrome.

BACKGROUND: The aim of this study was to determine the influence of environmental factors on the occurrence of overweight and obesity in children with Down syndrome. METHODS: The study was conducted in a group of children with Down Syndrome under the care of the Genetic Clinic in Gdansk from May 2017 to December 2018. RESULTS: The study included 26 female patients and 22 male patients with Down Syndrome, aged 7 to 18 years. The children were divided into two groups: group 1, with normal body weight and underweight; and group 2, with obesity and overweight. Overweight and obesity were diagnosed in 19% of children with Down Syndrome. The BMI analysis of the parents showed that the fathers of children with obesity and overweight had a higher BMI (P=0.043). In the group of children with overweight and obesity, obesity was more common in siblings (P=0.029), and sucking disorders were less frequent in the infancy period (P=0.015). Children with obesity and overweight were more likely to eat white bread (P=0.039), milk and other dairy products (P=0.04), and eggs (P=0.029) and ate more often between meals (P=0.022). CONCLUSIONS: In families of children with Down Syndrome affected by overweight and obesity, nutritional disorders were more frequent in the other members of the family. More frequent unhealthy dietary choices were found in children with Down Syndrome affected by overweight and obesity than in children with a normal body weight and underweight. It is necessary to educate families about the principles of a healthy lifestyle, as it can improve the quality of life of patients with Down syndrome and the whole family.

COVID-19 Pandemic-Knowledge, Attitudes, Behaviours, and Actions among Faculty of Health Sciences Students.

The aim of the study was to assess the level of knowledge about COVID-19 disease and preventive behaviour of undergraduate students of nursing, midwifery, and emergency medicine. MATERIAL AND METHODS: An electronic survey was conducted among students of nursing, midwifery, and emergency medicine during the COVID-19 pandemic, from 8 April 2021 to 6 June 2021 in the Pomeranian Voivodeship. RESULTS: A total of 37 men and 238 women participated in the study. A moderate level of knowledge was found in 88% and high in 11% of students Midwifery students had a higher level than nursing students (p = 0.002) and students of emergency medicine (p = 0.003). The female gender is much more afraid of SARS-CoV-2 virus infection (p = 0.021). The most common preventive measure was to avoid people who coughed or had a cold (93%). Only 84% of students were vaccinated. Students who had a high level of knowledge more often avoided people who coughed or had a cold (p = 0.03) and gave up on meeting with friends (p = 0.02). CONCLUSIONS: Constant education of students on the principles of dealing with the risk of infection with SARS-CoV-2 is necessary. It is important to continually motivate students to adhere to the principles of prevention. In the face of the existing epidemiological threat, there is a need to change the curricula for the fields of health sciences by adding the subject infectious diseases-clinic and nursing, with special attention to practical aspects.

Expression of BARD1 ß Isoform in Selected Pediatric Tumors.

Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is BARD1 (BRCA1 Associated RING Domain 1)-a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on BARD1 significance in childhood cancer is limited. This study determines the expression level of BARD1 and its isoform beta (ß) in three different histogenetic groups of pediatric cancer-neuroblastic tumours, and for the first time in chosen germ cell tumours (GCT), and rhabdomyosarcoma (RMS), using the qPCR method. We found higher expression of beta isoform in tumour compared to healthy tissue with no such changes concerning BARD1 full-length. Additionally, differences in expression of BARD1 ß between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of BARD1 ß characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the TERT (Telomerase Reverse Transcriptase) gene. In two RMS cases we found deep decrease of BARD1 ß in post-chemotherapy samples. This work supports the oncogenicity of the beta isoform in pediatric tumours, as well as demonstrates the differences in its expression depending on the histological type of neoplasm, and the level of maturation in neuroblastic tumours.

Dysgerminoma with a Somatic Exon 17 KIT Mutation and SHH Pathway Activation in a Girl with Turner Syndrome.

This article reports a case of a 7-year-old girl with Turner syndrome, treated with growth hormone (GH), who developed ovarian dysgerminoma. The patient karyotype was mosaic for chromosome Xq deletion: 46,X,del(X)(q22)/45,X. No Y chromosome sequences were present. Molecular studies revealed the presence of a driving mutation in exon 17 of the KIT gene in the neoplastic tissue, as well as Sonic-hedgehog (SHH) pathway activation at the protein level. The patient responded well to chemotherapy and remained in complete remission. This is the first case of dysgerminoma in a Turner syndrome patient with such oncogenic pathway.

Clinical characteristics and outcome of pediatric patients diagnosed with Langerhans cell histiocytosis in pediatric hematology and oncology centers in Poland.

BACKGROUND: Langerhans cell histiocytosis (LCH) affects 1-2 in 1,000,000 people. The disease is not associated with increased risk of treatment failure (especially among older children), but appropriate procedures implemented in advance can eliminate complications which might appear and significantly worsen the patients' quality of life. Thus, we sought to evaluate the clinical features, management, and outcome of children with LCH treated in Polish pediatric hematology-oncology centers. MATERIALS AND METHODS: One hundred eighty two patients with LCH were treated according to the Histiocytic Society Guidelines between 2010 and 2017. The participating centers were requested to provide the following data: demographic, clinical, as well as local or systemic treatment data and patients' outcome. Overall survival (OS) and event free survival (EFS) were estimated by Kaplan-Meier methods and compared using the log-rank test. RESULTS: Sixty nine percent of children were classified as single system (SS). The patients with SS disease were significantly older as compared to the children with multisystem disease (MS), 6 vs. 2.3 years respectively (p 0.003). Bones were involved in 76% of patients. Systemic treatment was applied to 47% of children with SS disease and 98% with MS disease. Fourteen patients relapsed while two children died. OS and EFS in entire group were 0.99 and 0.91 respectively (with median follow-up 4.3 years). CONCLUSION: The treatment of LCH in Polish centers was effective, however, new approaches, including mutation analyses and good inter-center cooperation, are needed to identify patients who might require modification or intensification of treatment.

Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer.

The tumor microenvironment (TME) consists of numerous biologically relevant elements. One of the most important components of the TME is the extracellular matrix (ECM). The compounds of the ECM create a network that provides structural and biochemical support to surrounding cells. The most important substances involved in the regulation of the ECM degradation process are matrix metalloproteinases (MMPs) and their endogenous inhibitors (tissue inhibitors of metalloproteinases, TIMPs). The disruption of the physiological balance between MMP activation and deactivation could lead to progression of various diseases such as cardiovascular disease, cancer, fibrosis arthritis, chronic tissue ulcers, pathologies of the nervous system (such as stroke and Alzheimer's disease), periodontitis, and atheroma. MMP-TIMP imbalance results in matrix proteolysis associated with various pathological processes such as tumor invasion. The present review discusses the involvement of two MMPs, MMP-2 and MMP-7, in cancer pathogenesis. These two MMPs have been proven in several studies, conducted mostly on adults, to make an important contribution to cancer development and progression. In the current review, several studies that indicate the importance of MMP-TIMP balance determination for the pediatric population are also highlighted. The authors of this review believe that carrying out biochemical and clinical studies focused on metalloproteinases and their inhibitors in tumors in children will be of great relevance for future patient diagnosis, determination of a prognosis, and monitoring of therapy.

Undifferentiated sarcoma of the liver: Multicenter international experience of the Cooperative Soft-Tissue Sarcoma Group and Polish Paediatric Solid Tumor Group.

BACKGROUND: Undifferentiated embryonal sarcomas of the liver (UESL) are extremely rare and continue to pose a diagnostic and therapeutic challenge. The aim of the study was to present a multicenter experience of the German CWS and Polish PPSTG groups in the treatment of UESL in children. PROCEDURE: Twenty-five patients were treated according to the CWS-96, CWS-2002, and CYVADIC protocols. Distant metastases were observed in four cases (16%). In four cases, an initial disease presentation mimicked other entities. A pure cystic appearance of liver mass led to misdiagnosis of hydatid cyst in three cases. In one case, laparotomy was performed due to the signs of appendicitis, and bleeding from ruptured liver tumor was found. All these patients were finally diagnosed as UESL. RESULTS: Thirteen patients received preoperative chemotherapy. Partial response was observed in 10 cases. Tumor resection was performed in 20 patients (primary resections, 12; delayed resections-, 8). In five patients, the primary tumor never became operable. The macroscopically complete resection rate was 95% (19/20). Postoperative chemotherapy was given to 20 children. Local radiotherapy was used in three children. After a median follow-up time of 136 months, 17 patients (68%) were alive with no evidence of disease. All children with unresectable tumor and three out of four patients with distant metastases died. The five-year overall survival (OS) rate was 72%. CONCLUSIONS: In summary, a complete tumor excision plays the central role in the treatment of UESL. A cystic presentation of the liver lesion on imaging does not exclude the diagnosis of malignant tumor.