From KIT-mutated into wild-type: dedifferentiation of gastrointestinal stromal tumor in adolescent patient-a case report.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs from adult-type disease in terms of histopathology and molecular features. Case Description: We describe the management of the disease in a 10-year-old female patient diagnosed with a GIST of the stomach. In total, she has undergone successively total tumor resection, unsuccessful imatinib treatment and subtotal gastric resection at relapse. The first genetic test from primary tumor confirmed KIT mutations in exons 13 and 17, while the repeated genetic screening using tumor sample from subtotal gastric resection revealed no KIT or platelet-derived growth factor receptor α (PDGFRA) genes mutations. Such dedifferentiation from adult type (thus KIT-mutated) into wild-type (without KIT or PDGFRA mutation) has not been reported so far to the best of our knowledge. Currently, the patient is observed, and no further pharmacological nor surgical treatment has been administered. Conclusions: The case underlines the importance of genetic profiling combined with non-standard diagnostics (both histopathological and radiological) due to the treatment efficacy prediction. We moreover emphasize the necessity to create worldwide standards on the diagnostics and treatment of GIST in pediatric patients that would include options of targeted therapies.

MRI and Pulmonary Function Tests' Results as Ventilation Inhomogeneity Markers in Children and Adolescents with Cystic Fibrosis.

Magnetic resonance imaging (MRI) of the chest is becoming more available in the detection and monitoring of early changes in lung function and structure in patients with cystic fibrosis (CF). The aim of this study was to assess the relationship between pulmonary function tests (PFT) and perfusion deficits in CF children measured by MRI. We performed a retrospective analysis of the perfusion lung MRI scans and the results of spirometry, oscillometry, body plethysmography, single-breath carbon monoxide uptake, and multiple-breath washout technique (MBW). There were statistically significant correlations between the MRI perfusion scores and MBW parameters (2.5% LCI, M1/M0, M2/M0), spirometry parameters (FEV1, FVC, FEF25/75), reactance indices in impulse oscillometry (X5Hz, X10Hz), total lung capacity (TLC) measured in single breath carbon monoxide uptake, markers of air-trapping in body plethysmography (RV, RV/TLC), and the diffusing capacity of the lungs for carbon monoxide. We also observed significant differences in the aforementioned PFT variables between the patient groups divided based on perfusion scores. We noted a correlation between markers of functional lung deficits measured by the MRI and PFTs in CF children. MRI perfusion abnormalities were reflected sooner in the course of the disease than PFT abnormalities.

How Does the Corrected Exhalyzer Software Change the Predictive Value of LCI in Pulmonary Exacerbations in Children with Cystic Fibrosis?

Aim: Recently, the most commonly used for multiple breath washout device, the Exhalyzer D, has been shown to overestimate lung clearance index (LCI) results due to a software error. Our study aimed to compare the predictive values of LCI in the CF pulmonary exacerbations (PE) calculated with the updated (3.3.1) and the previous (3.2.1) version of the Spiroware software. Materials and Methods: The measurements were performed during 259 visits in CF pediatric patients. We used 39ΔPE pairs (PE preceded by stable visit) and 138ΔS pairs (stable visit preceded by stable visit) to compare the LCI changes during PE. The areas under the receiver operating curves (AUCROC) and odds ratios were calculated based on the differences between ΔPEs and ΔSs. The exacerbation risk was estimated using a logistic regression model with generalized estimating equations (GEE). Results: There were statistically significant differences in LCI 2.5% median values measured using the two versions of the software in the stable condition but not during PE. The AUCROC for changes between the two consecutive visits for LCI did not change significantly using the updated Spiroware software. Conclusions: Despite the lower median values, using the recalculated LCI values does not influence the diagnostic accuracy of this parameter in CF PE.

Successful Treatment of Large B-Cell Lymphoma in a Child with Compound Heterozygous Mutation in the ATM Gene.

Ataxia-telangiectasia (AT) is a multisystemic neurodegenerative inborn error of immunity (IEI) characterized by DNA repair defect, chromosomal instability, and hypersensitivity to ionizing radiation. Impaired DNA double-strand break repair determines a high risk of developing hematological malignancies, especially lymphoproliferative diseases. Poor response to treatment, excessive chemotherapy toxicities, and the need for avoiding exposure to ionizing radiation make the successful clinical management of patients with AT challenging for oncologists. We describe the favorable outcome of the LBCL with IRF4 rearrangement at stage III in a 7-year-old female patient diagnosed with AT. The patient was treated according to the B-HR arm of the INTER-B-NHL-COP 2010 protocol, including the administration of rituximab, cyclophosphamide, methotrexate, prednisone, etc. She presented excessive treatment toxicities despite individually reduced doses of methotrexate and cyclophosphamide. However, in the MRI there was no significant reduction in pathologic lymph nodes after three immunochemotherapy courses. Therefore, a lymph node biopsy was taken. Its subsequent histopathological examination revealed tuberculosis-like changes, though tuberculosis suspicion was excluded. After two following immunochemotherapy courses, PET-CT confirmed complete remission. From March 2022 onwards, the patient has remained in remission under the care of the outpatient children's oncology clinic.

Latest Advances in the Management of Pediatric Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs biologically from adult-type diseases presenting mutations of KIT and PDGFR genes. In this population, more frequent is the wild-type GIST possessing SDH, TRK, RAS, NF1 mutations, among others. Both tumor types require individualized treatment with kinase inhibitors that are still being tested in the pediatric population due to the different neoplasm biology. We review the latest updates to the management of pediatric gastrointestinal tumors with a particular focus on the advances in molecular biology of the disease that enables the definition of possible resistance. Emerging treatment with kinase inhibitors that could serve as targeted therapy is discussed, especially with multikinase inhibitors of higher generation, the effectiveness of which has already been confirmed in the adult population.

Case Report: Brentuximab Vedotin Associated Acute Pancreatitis in a Pediatric Hodgkin Lymphoma Patient: Case Report and Literature Review.

Brentuximab vedotin is a conjugate drug used mainly in Hodgkin lymphoma, systemic and primary cutaneous anaplastic large cell lymphomas, and CD30-expressing peripheral T-cell lymphoma. We report a unique case of acute pancreatitis associated with brentuximab vedotin in a 17-year-old male patient suffering from classical Hodgkin lymphoma. Diagnosed in 2020, the patient was classified to an intermediate therapeutic group and disease's grade was IIIAE. The patient was treated with brentuximab vedotin and bendamustine in the third line. Two weeks after the drug administration, the patient developed acute epigastric pain. Laboratory and radiological findings confirmed the clinical suspicion of acute pancreatitis that was managed with opioid pain medications, meropenem, parenteral nutrition, ondansetron and omeprazole. This is the first case report of brentuximab vedotin-associated acute pancreatitis in the pediatric patient reported in the literature to the best of our knowledge.

Negative symptoms in schizophrenia, assessed by the brief negative symptom scale, self-evaluation of negative symptom scale, and social cognition: a gender effect.

OBJECTIVE: Negative symptoms of schizophrenia can be related to social cognition. The aim was to measure a relationship between the results on the new scales for the assessment of negative symptoms such as the Brief Negative Symptom Scale (BNSS) and Self-evaluation of Negative Symptoms (SNS), and the measures of social cognition. METHODS: The study included 80 patients (40 men, 40 women) with schizophrenia, aged 19-63 (mean 38 years), during the improvement period. They were assessed using the BNSS, SNS, Personal and Social Performance (PSP) scales, and the tests for social cognition such as the Facial Emotion Identification Test, Reading the Mind in Eyes Test, Strange Stories and Faux Pas Test. RESULTS: Male patients obtained higher scores than females when assessed by the BNSS. No gender differences were observed for the SNS scale. Female patients scored better in the PSP and both parts of the Faux Pas test and obtained a significant correlation between the results of the SNS scale, BNSS, PSP, and the affective part of the Faux-Pas test what was not the case in males. CONCLUSIONS: Gender differences were found in the assessment of negative symptoms by a clinical scale and the relationship between negative symptoms and social cognition.KEY POINTSFemale patients scored better in the BNSS, PSP and both parts of the Faux-Pas testGender differences were present in the assessment of negative symptoms by clinical (BNSS) but not the self-assessment (SNS) scale.Female patients obtained a significant correlation between the results of the SNS scale, BNSS, PSP, and the affective part of the Faux-Pas test what was not the case in male subjects.

Assessment of resting energy demand and body composition in oncological patients undergoing partial resections of the liver.

INTRODUCTION: The metabolism of the body is a complicated process. The most important organ of the organism that affects the intensity of changes is the liver. An effective treatment method of primary and metastatic tumours is a partial resection of the organ. The analysis of changes in the body composition of patients undergoing this type of treatment allows identification of problems coexisting with the underlying disease. AIM: To evaluate changes in the parameters of body composition and the amount of resting metabolism. MATERIAL AND METHODS: The study group consisted of 87 patients who underwent resection of changes in the liver or thermoablation of focal lesions during hospitalisation. RESULTS: Analysis of the data showed that the surgical intervention contributes to a statistically significant (p < 0.05) decrease in the value of the phase angle. A significant increase was noted within the extra cellular water content. The amount of resting metabolism in the postoperative period did not differ significantly; however, there was an upward trend in women and a downward trend in men. CONCLUSIONS: Surgical resection of lesions aimed at extending the survival of patients are performed more and more often, while the consequences of these operations are not sufficiently known. The adverse effect of resection treatments on body composition parameters, mainly imaged by decreasing the phase angle value, should be minimised. Effects on metabolism remain ambiguous because no significant changes have been demonstrated in the postoperative period.

Assessment of changes in the body composition in patients qualified for the operational treatment of the primary and metastatic liver tumors with the use of bioelectric impedance.

INTRODUCTION: Resection is an optimal way of treatment of hepatic tumors and metastasis from another organ. The operational injury may influence on patients body composition examined by bioelectrical impedance (BIA). Analysis of parameters may be helpful in identifying early changes indicating of deterioration in nutritional status. THE AIM OF THE STUDY: was to assess changes in body composition of patients before and after resection of liver tumors and potential radiofrequency ablation of lesions. MATERIAL AND METHODS: The study included a group of 50 patients of the Department of General, Gastroenterological and Oncological Surgery, Medical University of Warsaw, who were qualified for radical surgical treatment of tumors within the liver. Data on water content, fat, muscle and cell mass were analyzed. RESULTS: Comparing data obtained from patients before and after intervention in the liver, statistically significant (p <0.05) loss of intracellular water, muscle mass, cell mass, as well as adipose tissue, was demonstrated. The phase angle value in these patients also significantly changed, decreasing by an average of 0.61°. On the other hand, the increase in content was noted in the case of extracellular water. CONCLUSIONS: Surgical intervention within the liver causes noticeable, unfavorable changes in the body composition, as evidenced by the reduction in the value of muscle mass, as well as cellular mass, resulting in a decrease in the phase angle. Bioelectric impedance is a suitable method for assessing changes in body composition of patients undergoing liver resection and is useful in clinical practice. It is advisable to conduct further research in the group of patients undergoing invasive treatment of the liver due to: an increasing number of such operations and centers where this type of surgical intervention is performed.

[Disturbances of social cognition in schizophrenia and bipolar disorder--similarities and differences]. / Zaburzenia poznania spolecznego w schizofrenii i chorobie afektywnej dwubiegunowej--podobienstwa i róznice.

In the first part of the article, two aspects of social cognition, such as the Theory of Mind (ToM), i.e. the ability to infer about mental and affective states of other people, having both cognitive and perceptive aspects as well as empathy, i.e. the ability to understand other person's perspective and take an emotional response of the observer to the affective state of the other person, were presented. Next, research on social cognition in schizophrenia and bipolar disorder (BD) has been reviewed, and the disturbances, observed in these two illnesses were compared, with particular emphasis on studies investigating social cognition in both schizophrenia and BD. The results of studies show that ToM disturbances occur both in schizophrenia and BD patients, however, in schizophrenia they are of greater severity. As for empathy, patients with schizophrenia have significant disturbances of recognizing emotions, as well as of cognitive and affective empathy. Patients with BD do not have abnormalities in cognitive empathy, have lesser disturbances of emotion recognition disorder compared with schizophrenia and show a connection between disturbances of affective empathy and the course of the disease (time period after manic or depressive episode). Further exploration of these issues seems important in order to determine to what extent the disturbances of social cognition can influence social and professional life of patients. It is also a potential area for therapeutic interventions supportive to pharmacotherapy.