Nonspecific Gastrointestinal Symptoms as the First Sign of Ganglioneuroblastoma Intermixed-Case Report and Literature Review.

Nonspecific gastrointestinal symptoms remain a problem for pediatricians because, out of a thousand trivial cases, there are rare diseases that require in-depth diagnostics and extensive knowledge to identify them. These complaints may be caused by a neoplastic process. We present the case of a 5-year-old boy whose diagnostic pathway lasted about 3 months. He was admitted to hospital due to severe abdominal pain. Physical examination revealed a bloated, hard, and painful abdomen. In the standing X-ray, the features of intestinal obstruction were visualized. An ultrasound examination showed a possible malignant lesion in the location of the left adrenal gland. After the surgical removal of the pathological mass and histopathological examination, the diagnosis of ganglioneuroblastoma intermixed was made. This tumor, along with neuroblastoma, ganglioneuroma, and ganglioneuroblastoma nodular, belongs to neuroblastic tumors (NTs), which originate from primitive cells of the sympathetic nervous system. NTs are quite rare, but they are still the majority of extracranial solid tumors in children, and their symptoms often appear relatively late when the neoplastic process is already advanced. The purpose of this review is to present current information about ganglioneuroblastoma, with a special emphasis on nonspecific gastrointestinal symptoms as first sign of this tumor and its diagnostics.

Nodular lymphocyte predominant Hodgkin lymphoma: Experience of Polish Pediatric Leukemia/Lymphoma Study Group.

Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) is a rare clinical entity. To investigate NLPHL clinical course and treatment a survey was performed within Polish Pediatric Leukaemia/Lymphoma Study Group (PPLLSG) participating centers. A questionnaire was sent to all participating centers and analysis of clinical data was performed. From 2010 to 2019, 19 pediatric patients with confirmed NLPHL were registered in Poland. Median age of patients was 12.2 (5.5 - 17.8) years. NLPHL occurred mainly in males (n = 17). Most of the patients (n = 16) had early stage disease - Stage I (n = 6) and stage II (n = 10). Four of the six patients with stage I disease (I A, n = 5; I B, n = 1) underwent complete primary resection. One of these relapsed and was treated with CVP (cyclophosphamide, vinblastine, prednisone) chemotherapy. Two other patients who were not resected completely received CVP chemotherapy and no relapses were observed. Thirteen patients presented with unresectable disease. Of these, eight received three CVP chemotherapy cycles, and five were treated with other chemotherapy regimens. Three relapses were observed and these patients were further treated with chemotherapy and rituximab. One patient underwent autologous stem cell transplantation (auto-SCT). All patients remain alive. Five-year progression-free survival and overall survival for the entire group of patients was 81.6% and 100%, respectively. NLPHL treatment results are consistent with results noted in other countries. Early stage patients have very good outcomes with surgery and observation or low intensity chemotherapy, but this approach may be insufficient in advanced disease.

Salivary and serum concentrations of selected pro- and antiinflammatory cytokines in relation to oral lesions among children undergoing maintenance therapy of acute lymphoblastic leukemia.

Acute lymphoblastic leukemia is the most common type of childhood cancer, accounting for about 23% of all cancers diagnosed in this age group. The last stage of radical treatment is remission maintenance, during which hospitalization is not necessary. The lesions occurring in the oral cavity caused by medications and chemotherapy may also be directly related to hematological and systemic disorders. The aim of this study was to examine the levels of selected pro- and anti-inflammatory cytokines in saliva and serum of both patients undergoing remission maintenance and those after the cessation of therapy who reported to the hematology clinic of the Pediatric University Hospital in Lublin. The results were later analyzed in relation to the frequency of oral lesions and subjective intensity of oral complaints. The study revealed significant differences in salivary and serum concentrations of TNF-α and IL-10 between test and control groups. Oral lesions were more frequent in patients receiving therapy compared to the control group. Subjective afflictions described by the Visual Analog Scale (VAS) mean values were highest in the control group.

[Can children with Hodgkin's disease be treated with chemotherapy only?]. / Czy dzieci z choroba Hodgkina moga byc leczone wylacznie chemioterapia?

Currently over 90% of children and adolescents with Hodgkin's disease (HD) can be cured thanks to use of multidrug chemotherapy (CT) combined with involved-field radiotherapy (IF-RT). However, the intensive treatment may increase the risk of late complications which may impair the patients' quality of life. In order to decrease the incidence of late complications the protocol with limited use of IF-RT was introduced in centers of Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). This study presents the treatment results of patients treated with CT only in comparison with the therapy results of children treated with CT and IF-RT. From 1997 to 2006, 634 children (age: 2-22,5 years) with HD were treated in 14 oncological centers of PPLLSG. Majority of patients received CT (3-8 cycles of MVPP/B-DOPA) combined with IF-RT. In 45 patients with IA-IIA stages presenting favorable risk factors (small mediastinal tumor, peripheral nodular mass of a maximum diameter < 6 cm, involvement of less than three nodular regions, ESR < 50 mm after 1 h, histologic type other than lymphocyte depletion and very good treatment response assessed after 3 CT cycles) IF-RT was omitted. Among 634 children first complete remission (RC) was not achieved in 2.4% of patients. Relapses occurred in 24 children (3.9%). The rates of 5-year overall survival (OS), relapse-free survival (RFS) and event-free survival (EFS) were 97%, 96% i 92%, respectively. All patients treated with CT only remain in first CR. All serious late complications (including 7 second neoplasms) occurred in patients treated with CT combined with RT. Seven children died because of severe complications, among them two in first CR (aplastic anemia, sepsis). Our results show that the use of CT only in precisely selected group of patients with HD do not impair the treatment results and may decrease the risk of late life threatening complications. Treatment response assessment with the use of PET may in future increase the number of patients treated without RT and limit the need of the use of invasive diagnostic methods in patients with residual mass.

CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells.

UNLABELLED: Despite the very high percentage of long-term remissions in acute lymphoblastic leukemia (ALL) in children, some of them suffer from recurrence of the disease. New treatment modalities, e.g. effective geno- and immunotherapy are needed. The use of neoplasmatic cells to present tumor antigens is one of the approaches in cancer vaccines. ALL cells lack the expression of costimulatory molecules and are poor antigen presenting cells (APCs) for T-cell activation. CD40/40L interaction stimulates B-cells to proliferate, differentiate, upregulate costimulatory molecules and increase antigen presentation. The aim of the study was to test the hypothesis that ALL cells can be turned into professional APCs by CD40L activation. Children with B-cell precursor ALL were enrolled into the study. Mononuclear cells from bone marrow or peripheral blood were stimulated with CD40L and interleukin 4. RESULTS: 1) after culture we noted upregulation of all assessed costimulatory, adhesion and activatory molecules i.e. CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II; 2) CD40L activated ALL cells induced proliferation of allogeneic T-cells (measured by [(3)H]thymidine incorporation). These results confirm the possibility of enhancing the immunogenicity of ALL cells with the CD40L system and indicate that this approach can be used in immunotherapeutic trials.

[Clinical characteristics and therapy outcome in children with stage IV Hodgkin's lymphoma--the experience of two oncological centres]. / Charakterystyka kliniczna i wyniki leczenia dzieci z choroba Hodgkina w IV stadium zaawansowania--doswiadczenia dwóch osrodków onkologicznych.

UNLABELLED: The cure rate in children with Hodgkin's disease (HD), at present time exceeds 90% but the prognosis in stage IV HD is much worse. THE AIM of the study was to analyze the initial symptoms, course and results of oncological therapy in children with stage IV of Hodgkin's disease. MATERIAL AND METHODS: The analyzed group comprised of 15 patients with IV stage HD (M/F: 11/4, mean age: 12 years), treated from January 1993 to March 2005, in two Polish centres of paediatric oncology in Gdansk and Lublin. The diagnosis and therapy were carried out according to the current protocols approved by the Polish Paediatric Leukaemia / Lymphoma Study Group (PPGBCh). RESULTS: Mean duration of initial symptoms was 4.5 months, with most children presenting general symptoms of HD. At diagnosis, the involvement of mediastinal and/or hilar lymph nodes was found in nine patients, lung infiltrations in six, involvement of the spleen, liver and bones in five, three and one patient, respectively. The nodular sclerosis histopathological type of HD predominated. Poor response to standard treatment was observed in five children. One patient received additional cycles of chemotherapy MVPP/B-DOPA, four children were administered the 2nd line chemotherapy Salvage 95. One boy with very poor response to the 1st and 2nd therapy lines additionally underwent megachemotherapy with peripheral blood stem cells transplantation. Radiotherapy was given to 13 children. 13 out of 15 children are alive and free of disease with mean follow-up duration of 6 years. In two of them late complications affecting hormonal status, cardio-pulmonary disorders and chronic B and C hepatitis were observed. Two children died including one admitted in a very severe condition, after long-lasting medical history who died of neutropenia-related sepsis. The second boy died 12 months after stem cell transplantation because of a second neoplasm--acute myeloblastic leukaemia. CONCLUSION: Chemo- and radiotherapy implemented according to protocols approved by the PPGBCh for children with stage IV HD, result in complete remission in most patients. Diagnosis made at earlier stages would result in giving less aggressive therapy, connected with a lower risk of durable late complications.

Lower expression of mRNA for interferon-gamma in T helper cells of children with newly diagnosed lymphomas.

The complex interactions between cancer and host cells are far from being fully elucidated. Assessment of Th1/Th2/Th3/Tr1 balance is an interesting approach to explain immunological disturbances in lymphomas. The aim of our study was to assess mRNA for pro- and anti-inflammatory cytokines in T-cells in 20 children with Hodgkin- and non-Hodgkin lymphomas. CD4+ and CD8+ cells were isolated from whole peripheral blood and four different cytokine mRNA levels (IFN-gamma, IL-10, IL-4, TGF-beta) were determined by real-time PCR technique. Comparing to the control group, we found lower expression of mRNA for IFN-gamma in CD4+ cells at the time of lymphoma diagnosis. It may be one of the pathogenetic mechanisms of impaired immunity in these patients.

Monocytes in children with leukemias and lymphomas -- down-regulation of HLA and costimulatory molecules.

The aim of the study was to evaluate the function of monocytes in children with leukemias and lymphomas based on the expression of critical costimulatory, activatory and adhesion molecules (CD80, CD86, HLA-DR and CD54 = ICAM-1), estimated with tricolor flow cytometry. In comparison to the control group we found a lower percentage of monocytes with costimulatory molecules (CD80 before and CD86 after lipopolysaccharide stimulation) at the time of diagnosis and of monocytes with HLA-DR molecules after remission induction. We also noted a lower percentage of monocytes with HLA-DR expression in the group with severe or therapy resistant infections. The results of our investigation suggest some defect in costimulation and antigen presentation in lymphoproliferative diseases in children.

[Second neoplasm in a 13-year-old boy complicated by Crohn's disease. Case report]. / Drugi nowotwór powiklany choroba Crohna u 13-letniego chlopca. Opis przypadku.

UNLABELLED: Genetic abnormalities and immune system disorders resulting from them are the causes of neoplastic diseases as well as inflammatory bowel disease, including Crohn's disease. However, the rearrangement of genes may not only be the cause of neoplasms but also the result of oncolytic treatment used. One of the late treatment-related complications of neoplastic diseases is the development of a second neoplasm and possible disorders belonging to the group of inflammatory bowel diseases, for example Crohn's disease. The paper presents the case of a 13-year-old boy (K.G.) treated for a second neoplasm, complicated by Crohn's disease. The patient was diagnosed with acute lymphoblastic leukaemia -- middle risk group (ALL-MRG) at the age of 3, treated according to the BFM 87 Protocol (dexamethasone, prednisone, vincristine, daunoribicin, asparaginase, cyclophosphamide, cytarabine, mercaptopurine, methotrexate, thioguanine, doxorubicin), and complete remission was achieved. Eight years after the first line treatment the boy was diagnosed with the second neoplastic process -- pre-B acute lymphoblastic leukaemia (ALL-L2 pre-B common +). The ALLIC 2002 Protocol (dexamethasone, prednisone, vincristine, daunoribicin, asparaginase, cyclophosphamide, cytarabine, mercaptopurine. methotrexate, thioguanine, doxorubicin) was started. On day 71 of the therapy, during aplasia of blood marrow following chemotherapy, inflammation of the caecum was diagnosed and metronidazole was introduced. Once blood counts improved, the complaints decreased and with continued chemotherapy of Protocol M (mercaptopurine, methotrexate), completely subsided. The symptoms reappeared during the 2-week break before Protoco II. The physical examination revealed the presence of a hard, painless tumour (3 x 10 cm) in the right iliac fossa. Colonoscopy showed a cauliflower-like formation within the Mauchin's valve projecting to the caecum lumen. The histopathological evaluation of the sections demonstrated a typical picture of Crohn's disease. Crohn's disease of the ileum was diagnosed, the treatment with dexamethazone (according to Protocol II) was instituted which led to complete regression of the iliac lesions. Steroid therapy (prednisone) continued until the treatment supporting the remission according to Protocol ALLIC 2002 (mercaptopurine, methotrexate orally) was initiated. CONCLUSION: The differential diagnosis of complications accompanying neoplasms should consider the inflammatory bowel diseases; their atypical course may be masked by the treatment of the underlying disease.

[Diagnostic and therapeutic management of essential thrombocythemia in children]. / Postepowanie diagnostyczno-lecznicze u dzieci z nadplytkowoscia samoistna.

BACKGROUND: Essential thrombocythemia is a myeloproliferative disease resulting from the clonal proliferation of a multipotent myeloid stem cell with an increased platelet count in peripheral blood. In 2% of cases the cause remains unknown. It is then called idiopathic essential thrombocythemia. THE AIM: The objective of this study was to present the diagnostic and therapeutic management of essential thrombocythemia in children. MATERIAL AND METHODS: The authors analysed complete medical records of 5 patients treated for essential thrombocythemia in the Department of Children Haematology and Oncology, Medical University Lublin during a 6 years (1996-2002) period. The investigated group consisted of 5 children: 3 boys and 2 girls with mean age of 7 years and 8 months (varying from 5 years and 3 months to 11 years and 8 months). RESULTS: The peripheral platelet count was above 1200 x 10(9)/L. Three patients developed functional symptoms of microvascular blood flow alteration (headaches, sensory disorders. paresthesiae). In 2 patients thrombocythemia was asymptomatic and the diagnosis was made incidentally. Diagnosis of essential thrombocythemia was made according to the criteria of the Polycythemia Vera Study Group and treatment with anagrelide hydrochloride was started. One patient due to bad drug tolerance was treated with hydroxyurea. Treatment of essential thrombocythemia in all patients resulted in: (1) decreased (500-600 x 10(9)/L) platelet count in peripheral blood; (2) resolving the symptoms of small vessels obturation (headaches, sensory disorders, paresthesiae); (3) low platelet separating megakaryocytes count in control myelograms (4) no transformation into acute neoplastic disease. CONCLUSIONS: In the treatment of children with essential thrombocythemia anagrelid was effective in four of five patients.

[Costimulatory and activation molecules of lymphocytes T in acute lymphoblastic leukemia in children]. / Czasteczki kostymulujace i aktywacyjne limfocytów T w ostrej bialaczce limfoblastycznej u dzieci.

UNLABELLED: In the last years one rises importance of costimulatory molecules in immune response in leukemias. Aim of the study was to assess lymphocytes T function in children with acute lymphoblastic leukemia during remission induction on the grounds of chosen costimulatory and activatory molecules expression. To assess percentages of lymphocytes subpopulations we used tricolor flow cytometry. RESULTS: 1. In the moment of diagnosis and remission induction we noted higher percentages of lymphocytes T with adhesion molecule ICAM-1; 2. During remission induction we observed lower percentage values of lymphocytes T with CD38 coexpression; 3. In the end of remission induction rised the percentage values of lymphocytes T helper with IL-2 receptor expression; 4. In the group of patients with fever/infection we observed higher percentage of activated lymphocytes T (CD3-HLA-DR) comparing to non-infected patients. Summarizing, we suggest lymphocytes T activation during appearance and remission induction of acute lymphoblastic leukemia in children. This confirms participation of cellular immunity in leukemic process.

[Th1/Th2 balance in acute lymphoblastic leukemia in children]. / Równowaga limfocytów Th1/Th2 w ostrej bialaczce limfoblastycznej u dzieci.

Analysis of T lymphocytes cytokine profiles allows to differ subpopulations: Th1, Th2, Th3, Tr1. Aim of the study was to assess Th1/Th2 balance in acute lymphoblastic leukemia in children at diagnosis and during/after remission induction, especially during infections. Percentages of lymphocytes T producing IFN-gamma and IL-4 were assessed by flow cytometry. We noted the rise of lymphocytes T helper producing IFN-gamma (Th1) and percentage of lymphocytes T producing IL-4 at the beginning and during remission induction was higher than in control group. During fever/infection we observed the rise of lymphocytes Th1, and no change in Th2 percentage. Summarizing we suggest Th1/Th2 imbalance and Th2 predominance in acute lymphoblastic leukemia in children.