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The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.

The unbalanced secretion of biogenic amines (BAs) is considered to be a relevant biochemical biomarker in the screening for neuroendocrine tumors, such as: neuroblastoma and pheochromocytoma. However, there is still a need to improve the bioanalytical procedures for BA determination in biological samples due to their instability (photo- and thermosensitivity, easy oxidation) and low concentration in the body fluids. In this study, the primary analytical challenge was to optimize the method of extraction of seven compounds from among BAs and their precursors from urine samples. Several methods based on liquid-liquid extraction (LLE) or solid phase extraction (SPE) techniques were tested. By optimization of the extraction and data analysis using chemometric tool, the dispersive liquid-liquid microextraction (DLLME) has been chosen due to its low solvents consumption, high efficiency of isolation, preconcentration and suitable clean-up of biological matrix. Further, α-cyclodextrin-modified micellar electrokinetic chromatography (MEKC) with ultraviolet detection (UV) has been applied for quantification of the analyzed biologically active compounds with limits of detection (LOD) and limits of quantification (LOQ) at 0.15 and 0.5μgmL-1, respectively. Finally, the optimized and validated DLLME-MEKC-UV method has been employed for the analysis of real urine samples, obtained from 6 children with neuroendocrine tumors and 6 healthy children. It was stated that concentrations of BA could serve to differentiate between the patients and healthy children. This pilot study indicates that the elaborated fast and sensitive DLLME-MEKC-UV method for determination of panel of biomarkers could be successfully applied in everyday clinical practice to help to confirm the clinical diagnosis of neuroendocrine tumors in children.

Introduction: Basal cell carcinoma (BCC) is an immunogenic neoplasm and the imbalance in Th1/Th2 cytokines expression seems to play the major role in pathogenesis and clinical behaviour of the tumour. Aim : To investigate the association of soluble interleukin 2α receptor (sIL-2Rα) and interleukin-2 (IL-2) serum concentrations with BCC. Material and methods : The study involved 110 individuals with BCC and 60 healthy age- and sex-matched volunteers. Serum levels of sIL-2Rα and IL-2 were measured using ELISA test. Results : We found significantly (p = 0.027) increased sIL-2Rα serum levels in BCC patients, in comparison to healthy controls. Statistically (p = 0.04) higher sIL-2Rα levels were observed in patients with more advanced tumours. Serum levels of sIL-2Rα showed a significant linear (r = 0.24, p = 0.018) correlation with tumour size. The average IL-2 serum levels in BCC patients were statistically (p = 0.039) decreased compared to controls. Significantly (p = 0.0454) lower median IL-2 levels were observed in patients with more advanced tumours. A negative correlation between sIL-2Rα and IL-2 serum concentrations was revealed (r = –0.22; p = 0.027). Conclusions : Our results testify to the importance of the IL-2/sIL-2Rα signalling pathway in pathogenesis of BCC, suggesting that IL-2 and sIL-2Rα might be considered as potential markers of disease and targets for immunotherapy in BCC patients.

The coexistence of two rare conditions in the same patient is a challenge. This paper reports on a case of a 14.5-year-old boy diagnosed concurrently with latent tuberculosis infection (LTBI) and a nasopharyngeal carcinoma (NPC). The initial symptom was the enlargement of the right cervical lymph nodes. Ultrasound imaging was initially suggestive of LTBI. A positive skin tuberculin test and positive serological examination with interferon gamma release assays were conducted. However, the histopathological examination of the lymph nodes biopsy did not reveal acid-fast bacilli. Therefore, the diagnosis of LTBI was set. Histopathological examination of lymph nodes biopsy showed metastases of NPC. The primary tumour was revealed by magnetic resonance imaging in the nasopharynx. Based on the results of the positron emission tomography combined with computer tomography, the patient was classified to the stage IVB according to clinical classification of head and neck carcinomas (UICC/AJCC TNM 7 from 2009). Due to an advanced stage of NPC, intensive chemotherapy followed by a combined chemo-radiotherapy was initiated according to NPC-2003-GPOH protocol. Concurrently a chemoprophylactic treatment of tuberculosis infection, using isonicotinylhydrazide (INH) and rifampicin (RMP) was conducted. During treatment hepatotoxicity stage IV WHO was noted, which did not allow for the continuation of chemotherapy. Anti-tuberculosis medications were identified as the cause of this complication. Withdrawing INH and RMP led to normalisation of aminotransferase levels and enabled further oncological treatment. Treatment was finished and the patient currently remains cancer-free. A three-month period of anti-tuberculosis chemoprophylaxis was sufficient. In imaging investigations, there are no signs of tuberculosis.

Exosomal heat shock proteins (Hsps) are involved in intercellular communication both in physiological and pathological conditions. They play a role in key processes of carcinogenesis including immune system regulation, cell differentiation, vascular homeostasis and metastasis formation. Thus, exosomal Hsps are emerging biomarkers of malignancies and possible therapeutic targets. Adolescents and young adults (AYAs) are patients aged 15–39 years. This age group, placed between pediatric and adult oncology, pose a particular challenge for cancer management. New biomarkers of cancer growth and progression as well as prognostic factors are desperately needed in AYAs. In this review, we attempted to summarize the current knowledge on the role of exosomal Hsps in selected solid tumors characteristic for the AYA population and/or associated with poor prognosis in this age group. These included malignant melanoma, brain tumors, and breast, colorectal, thyroid, hepatocellular, lung and gynecological tract carcinomas. The studies on exosomal Hsps in these tumors are limited; however; some have provided promising results. Although further research is needed, there is potential for future clinical applications of exosomal Hsps in AYA cancers, both as novel biomarkers of disease presence, progression or relapse, or as therapeutic targets or tools for drug delivery.

The aim of the work was to develop a simple, sensitive and accurate liquid chromatography with fluorescence detection (LC-FL) method for the determination of epirubicin in human urine and plasma. Solid phase extraction with HLB cartridges and mixture of dichloromethane:2-propanol:methanol (2:1:1, v/v/v) as the eluent, was used to prepare the samples. The chromatographic analysis was carried out on a Synergi Hydro-RP column with a mobile phase consisting of 40 mM phosphate buffer (pH 4.1) and acetonitrile (69:31, v/v). Epirubicin was monitored at 497 nm and 557 nm for excitation and emission wavelengths, respectively. Validation data confirmed that the limit of detection and limit of quantification was 0.25 ng/mL and 0.5 ng/mL in both matrices. Next, the optimized LC-FL method was applied to determine the level of epirubicin in real samples taken from a 19-year-old patient with metastatic alveolar rhabdomyosarcoma (RMA) to create a drug profile. Plasma and urine samples were collected for 24 h after the end of a 6-hour infusion of epirubicin. The obtained results confirmed that the optimized and validated LC-FL method can be successfully used in drug monitoring therapy, pharmacokinetic and clinical studies. Moreover, the current work is also drawing attention to the relatively high level of epirubicin in the patient urine, which requires compliance with the safety rules in contact with this biological fluid by both medical staff and others, e.g. family members.

Objectives: The analysis of epidemiology, risk factors and outcome of infections in children with malignant bone tumors (MBT) undergoing chemotherapy. Methods: In this retrospective nationwide multicenter cross-sectional study, a total number of 126 children with MBT including 70 with Ewing sarcoma (ES) and 56 with osteosarcoma (OSA) were screened for infections over a period of 72 consecutive months. Results: The risk of infection was 7.15-fold higher in patients with ES as compared to the OSA group, especially concerning bacterial infections (4.1-fold increase risk). Bacterial infections occurred in 74.3% patients with ES and in 41.1% with OSA. The median time from diagnosis to first infection was 4.9 months. 33.0% of bacterial episodes were diagnosed as bloodstream (BSI), 31.1% as gastrointestinal tract, 30.1% as urinary tract infection. Infection-related mortality (IRM) from bacterial infection was 6% and 15% in ES and OSA patients, respectively. Cumulative incidence was 7.1% for invasive fungal disease and 6.3% for viral infections. The only significant risk factor for IRM was time to infection ≥5 months since the beginning of chemotherapy. All patients who have died from infection had BSI and were in neutropenia. Conclusions: Infections in the children with MBT in our study occurred with high frequency, especially in patients with ES. The most frequent were bacterial infections, while fungal and viral infections were episodic. Among the bacterial infections, bloodstream, urinary tract and gastrointestinal tract infections occurred with similar frequency. All deceased patients died due to BSI. Bacterial infection occurring ≥5 months since the beginning of chemotherapy was a risk factor for death.

This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing.

The main aim of the presented study was to develop a reliable and non-time-consuming method for the simultaneous separation of biogenic amines (BAs) like noradrenalin, adrenalin, dopamine and their main metabolites - homovanillic acid (HVA), vanillylmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC) - in urine samples. To achieve this, the validated α-cyclodextrin (α-CD)-modified micellar electrokinetic chromatography method with DAD was proposed. The optimized separation parameters were as follows: background electrolyte was composed of 10mM sodium tetraborate decahydrate, 30mM SDS, 15% (v/v) methanol and 25mM α-CD, adjusted to pH 9.36 with 1N NaOH; uncoated fused silica capillary (75μm i.d.×60.2cm length); λ=200nm; injection time 5s, applied voltage 25kV; temperature 25 (±0.1)°C. Next, the developed MEKC method was practically applied to evaluate the levels of selected acidic metabolites of catecholamines like HVA, VMA and DOPAC in urine samples collected from patients diagnosed with neuroblastoma (NB), melanotic neuroectodermal tumor of infancy (MNTI).

Infections in children treated for hematological malignancies pose a direct threat to life and are one of the most common causes of treatment failure in this group of patients. Unequivocal diagnosis at the early stages of infection together with an appropriate and timely treatment may be often difficult due to poor manifestation and nonspecific clinical symptoms of the infection progress. Inflammatory markers make a useful diagnostic tool for this purpose. They significantly help to diagnose, monitor, stratify and predict the outcome in severe infections. This article describes selected biomarkers, both those commonly used in clinical practice, such as erythrocyte sedimentation rate, C-reactive protein, procalcitonin as well as less common like IL-6, IL-8 and moreover one promising novel marker – pentraxin 3. The authors emphasize their diagnostic value, clinical usefulness and significance in the treatment efficacy monitoring.

Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology and varied picture and clinical course. The intensity and the outcome of LCH treatment depend on the amount and type of the affected organs, their dysfunction and age of the patient. In this paper we present the diagnostic difficulties in a 19-month-old girl with multisystem LCH, manifesting mainly by persistent fever, deep anemia, hepatosplenomegaly and lymphadenopathy, coexisting with EBV infection and urinary tract infection. On diagnosis, LCH was suspected once the bone lesions were detected on CT scans, which, however, were not confirmed in the bone scintigraphy. Histopathological diagnosis of LCH was based on the histopathological examination of the cervical lymph node, in which CD1a expression was detected. Myelogram morphologically was assessed as normal; however, bone marrow smears were respectively found to express CD1a. The patient received aggressive and long-lasting treatment according to the protocol LCH in 2009, yielding a complete clinical remission of LCH.

Although childhood rhabdomyosarcoma typically metastasizes to lungs, various processes may mimic metastatic etiology. Described herein is the case of an 8½-year-old boy with orbital embryonal rhabdomyosarcoma (RME) in whom three small foci were detected within both lungs on computed tomography. The lesion number and size, however, did not fulfil the Cooperative Weichteilsarkom Study Group 2006 protocol criteria for lung metastasis. Chemotherapy for localized RME produced primary tumor regression and vanishing of the left lung lesion. Two lesions in the right lung remained unchanged. On thoracoscopy multiple minute nodules disseminated in both lungs were detected. Histopathology excluded RME spread but indicated anthracosis in the lung parenchyma and intrapulmonary lymph nodes. Heavy smoking by parents and previous home furnace combustion appeared to be predisposing factors. Uncommon non-malignant intrapulmonary diseases, including anthracosis, should be considered when staging pediatric cancer.

Introduction Cutaneous melanoma is rare in childhood and published studies have mainly been retrospective single-institution series or small case series. Given the absence of clinical protocols dedicated to pediatric melanoma, the treatment approach is generally extrapolated from the ones applied to adults. Methods Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), this study collected patients prospectively registered between 2002 and 2012 under national cooperative projects dedicated to rare pediatric tumors in Italy, Poland, Germany, and France. Additional cases were collected from dermatology registries in Germany and Israel. Results A total of 219 patients aged 0-18 years (median 14.4) were included in the analysis. Sentinel lymph node biopsy was performed in 112 patients (76% of those with Breslow thickness > 0.75 mm) and was positive in 37.5%. Systemic therapy was used in 33 cases. In stage III cases, survival rates were similar for patients who received (23 cases) or not (21 cases) adjuvant therapy. For the whole series, 3-year overall and disease-free survival rates were 91.4% and 84.0%, respectively (median follow-up 41.8 months). Tumor site, tumor stage, and ulceration influenced survival rates. Patients treated by pediatric oncologists (n = 140) were more likely to have advanced disease than those treated by dermatologists (n = 79). Discussion This study would suggest that the clinical history of melanoma in children and adolescents might resemble that of adult counterpart. Cooperative efforts are needed to make new drugs more readily available to pediatric patients to increase the outcome of patient with advanced disease.

Objective: Osteopontin (OPN) is aglyco-phosphoprotein, involved in tissue remodeling, inflammation and boneresorption. In various adult neoplasms OPN was shown to correlate with cancer progression, invasiveness and metastasis. Aim: to define the role of OPN in malignancies of children and young adults. Material and methods: a structured PubMed and Google Scholar literature analysis based on reports published in English between I'1995 and XII'2015. Results: 14 studies (four on hematological malignancies, four on bone tumors, three on CNS tumors, two on dendritic proliferative diseases and one on renal tumors) were identified. Higher levels of serum and cerebro-spinal fluid OPN protein, and high expressions of OPN mRNA and SPP1 gene were present in more aggressive and advanced childhood malignancies. In children with acute lymphoblastic leukemia with CNS involvement and with atypical teratoid/rhabdoid tumor (AT/RT) and medulloblastoma, the serum and CSF OPN levels reflected tumor bulk and response to therapy, while in children with AT/RT and multisystem Langerhans cell histiocytosis with high-risk organs involvement, high OPN serum levels correlated with poorer survival. To the contrary, in osteosarcoma, high OPN mRNA and SPP1 gene expressions correlated with better survival and good response to chemotherapy. Conclusions: The literature review suggests that OPN may play important roles in the development and progression of selected cancers of children and young adults, including acute lymphoblastic leukemia, malignant gliomas, AT/RT and Langerhans cell histiocytosis. However, limited number of published studies prevents from definite concluding on the clinical utility of OPN as a marker of diagnosis, prognosis and treatment monitoring in these pediatric cancers. Further studies performed in more numerous groups of patients with particular types of cancers of children and young adults are warranted.

Hepatic angiosarcoma is a rare, aggressive, malignant neoplasm with fewer than 50 cases reported in children. Prognosis is poor, with a minority surviving beyond 2 years after diagnosis. We report eight cases of pediatric hepatic angiosarcoma, diagnosed at a mean age of 3 years. Seven were initially diagnosed with an infantile hepatic hemangioendothelioma (IHHE) or hemangioma and the eighth with a "vascular tumor." Two patients, who received liver transplant, survived. We suggest hepatic hemangiomas can rarely transform into angiosarcomas and a subset of IHHEs (Type II) are actually a low-grade form of angiosarcoma rather than a benign lesion.

Neuroblastic tumors (NB) are the most common extracranial pediatric neural crest-derived tumors, with a dismal outcome in a substantial group of patients. The study objective was to evaluate the patho-clinical correlations and prognostic impact of the proliferation index (PI) measured with two markers, Ki67 and topoisomerase II alpha (Topo2A), in a NB series. A retrospective analysis of 118 NB from 103 consecutive patients was performed. Analyzed data included tumor stage, histology, mitosis/karyorrhexis index (MKI), MYCN status, and overall survival. Patients' median follow-up period was 50 months. Ki67 and Topo2A PI were assessed immunohistochemically on representative tissue slides in hot spots. PI for Ki67 was in the range 0-72% (median 18%) and for Topo2A was in the range 0-58% (median 20%), being strongly interrelated (r = 0.83). Median PIs with both markers were lower in children older than 18 months (> 18 m) than in the younger patients, with p = 0.0002 and p = 0.005 respectively. Higher Ki67 and Topo2A correlated with metastatic stage, higher MKI, and inversely with increasing tumor differentiation. The cut-off values of PI Ki67 > 30% and Topo2A > 20% were associated with fatal outcome of the disease. In the subgroup of patients > 18 m already at cut-offs Ki67 > 10% and Topo2A > 15% a fatal outcome was predicted by Kaplan-Meyer analysis. Cox regression analysis identified cumulative PI (joint Ki67 and Topo2A index) as an independent prognostic factor. The conclusion is that the proliferation index measured with the examined markers provides substantial prognostic information in NB, especially in infants. PI assessment should become an element of the standard pathological checkup list of NB tumors.

Introduction: Pre-treatment serum IL-10/IL-12 balance has been recently found deregulated in childhood soft tissue sarcomas (STS). Its role in STS monitoring and assessment of response to therapy is unknown.Objective: To establish whether serum IL-10 and IL-12 levels and their reciprocal ratios reflect childhood STS course and actual activity and whether G-CSF therapy and central vein catheter (CVC)-related sepsis influence the interleukins levels.Materials and methods: ELISA determinations of serum interleukins were performed before treatment, in remission without complications (CR), at relapse and after treatment in 59 STS patients and during G-CSF administration and CVC-related sepsis (in 18) and also in 30 healthy controls. Results: In CR IL-10 declined and IL-12 increased as compared to pretreatment levels; in relapse IL-10 rose and IL-12 decreased significantly as compared to levels in CR. Also rates of IL-10, IL-12, and IL-10/IL-12 ratios recently estimated by us as of prognostic significance reflected well the STS course. During G-CSF therapy and CVC-related sepsis, IL-10 increased and IL-12 decreased significantly from levels in CR without complications. IL-10 levels and rates of IL-10 ≥11 pg/ml in sepsis could falsely suggest relapse. However, IL-12 levels, rates of IL-12 ≤60 pg/ml and/or simultaneous determination of both interleukins differed significantly from levels at relapse. Conclusion: Serial determinations of serum IL-10 and IL-12 reflected well the course of STS in children and enabled remission and relapse phases to be distinguished. To avoid G-CSF and sepsis influence, IL-12 and IL-10/IL-12 ratio and not IL-10 alone should be analysed.

Objectives The aim of this retrospective international analysis was to evaluate the role of risk factors in pediatric patients with adrenocortical carcinoma (ACC) observed in European countries (2000–2013) in an attempt to identify factors associated with poor prognosis. Procedures Data were retrieved from databases of Germany, France, Poland, and Italy, which form the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT). Patients were less than 18 years old, with at least one of the following tumor-related risk factors: metastases, volume more than 200 cm3, Cushing syndrome, vascular or regional lymph node invasion, initial biopsy, or incomplete excision. Role of patients’ age was also evaluated. Results Eighty-two patients were evaluated: 62 with localized disease and 20 with metastases. The 3-year progression-free survival (PFS) and overall survival (OS) were 39% and 55% for the whole population, respectively, and 51% and 73% for localized diseases, respectively. Concerning the whole population, PFS and OS were influenced by distant metastases, tumor volume, lymph node involvement, age, and presence of two or more risk factors. Factors significant only at OS were vascular involvement and incomplete surgery. At multivariable analysis, the main factors at PFS were volume more than 200 cm3 (hazard ratio [HR]: 2.6, 95% confidence interval [CI]: 1.18–5.70) and presence of distant metastases (HR: 8.26, 95% CI: 3.49–19.51). The OS was significantly influenced by the presence of metastases (P < 0.0001). Concerning patients with localized tumors, the only significant prognostic factor was volume more than 200 cm3 with a HR of 4.38 (95% CI: 1.60–12.00) for PFS and of 3.68 (95% CI: 1.02–13.30) for OS. Conclusions Distant metastases and large tumor volume were the main unfavorable prognostic factors. Presence of two or more factors related to ACC was associated with an aggressive behavior of disease.

Purpose. Langerhans cell histiocytosis (LCH) is an infrequent disorder of unknown origin associated with histiocytic proliferation. The bones' involvement (including cranial bones) is the most frequent manifestation of pediatric LCH. Imaging of skull LCH is based predominantly on conventional radiography, CT, scintigraphy, and sometimes MRI. The aim of the study was to investigate the role of sonography (US) in the diagnosis and monitoring of bone lesions in children with localized LCH of the skull. Methods. Twenty-seven children (15 boys/12 girls, mean age 6.1 years) were diagnosed between 1991 and 2005 in the Department of Pediatrics at the Medical University of Gdansk, Poland. Fourteen children (52%) had localized LCH of the skull. Results. All lesions of the skull visible on CT were visualized on US examination. Overall, 30 focal lesions were revealed by US. The largest bone lesions were accompanied by changes within the adjacent soft tissues. CT revealed 26 lesions, the location and size of which corresponded to the lesions seen on US, but soft-tissue changes adjacent to the bony lesions were difficult to visualize. Conclusions. The US appearance of focal LCH lesions in cranial bones in children is not pathognomonic, but is characteristic enough to suggest an initial diagnosis and to monitor the evolution of lesions during treatment. US should be considered an additional diagnostic tool for LCH of the skull. Although US of localized LCH cannot replace CT, it could reduce the number of follow-up CT examinations. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2013

Many components of oncologic treatment increase serum sIL-2Rα level, which may falsely suggest a relapse. We tried to establish whether granulocyte colony stimulating factor (G-CSF) and central vein catheter (CVC)-related sepsis increase serum sIL-2Rα level to values on relapse of childhood soft tissue sarcomas (STS) and how to distinguish real relapse from a "false" one. Serum sIL-2Rα, B2-M, LDH, CRP and ESR levels and rates of markers' elevated values were determined prospectively in 18 STS children: pre-treatmently (ST1), in complete remission (CR; ST2), in CR during G-CSF therapy (ST3), in CR during CVC-related sepsis (ST4), on relapse (ST5) and after treatment (ST6) and once in 50 healthy pediatric controls. It appeared that pre-treatment serum sIL-2Rα, LDH, CRP and ESR but not B2-M declined significantly with remission (ST2) achievement. At ST5 sIL-2Rα, B2-M, LDH and CRP increased from ST2 to ST1 values. SIL-2Rα levels at ST3 and ST4 rose significantly in all patients from ST2 to ST1 and ST5 values. At ST3 also serum LDH and B2-M increased to values at ST1 and ST5 and exceeded significantly those at ST2 and ST4. At ST4 CRP but not B2-M and LDH, rose significantly in most patients to values at ST1 and ST5. Thus, serum sIL-2Rα monitoring in pediatric STS reflects well response to chemotherapy unless samples are collected during G-CSF therapy or CVC-related sepsis. Determination of serum B2-M, LDH and CRP together with sIL-2Rα may help to distinguish between "real" relapse and "false" sIL-2Rα increase due to G-CSF administration or CVC-related sepsis.

HER receptor family plays an important role in normal embryonic development and is involved in pathogenesis and progression of some types of cancer. Neuroblastic tumors (NT) are common pediatric neoplasms with a poor outcome in a significant number of patients. The biological and prognostic role of HER family in NT is not well established. In the current study we evaluated HER1-4 receptors expression, their prognostic significance and clinicopathological correlations in a series of 103 NTs by immunohistochemical assessment of HER1-4 expression and FISH analysis of EGFR and HER2 copy number status. HER receptors are commonly expressed in NT but it was not due to EGFR or HER2 amplification. EGFR, HER2 and HER4 show correlation with tumor histology. It seems that these receptors take part in neuroblastic cell differentiation and Schwannian stroma development. EGFR and HER2 positivity are more frequently found in favorable histological risk group of tumours (P = 0.004 and P = 0.01 respectively) while high expression of HER4 is significantly more often found in patients with metastatic disease (P = 0.03). Moreover tumors with HER2 polysomy were more often found in children ≤ 18 months, with localized disease, and favorable histological group. Our study showed that the role of HER family members in NT biology is interrelated and complex but their expression level may present a novel prognostic factor for NT patients outcome.

The rarity of malignant and intermediate vascular tumors in children means that little is known about their clinical course, optimal treatment, and variables predicting survival. A total of 32 children with malignant vascular tumors (14 angiosarcomas [AS], 5 epithelioid hemangioendotheliomas, and 13 intermediate vascular tumors, including other hemangioendotheliomas plus adult-type hemangiopericytomas), registered in the German and Polish Paediatric Soft Tissue Sarcomas Study Groups, were treated following the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, -86, -91, and -96 protocols. Male sex, AS histology, tumor size >5 cm, and T2 invasiveness were independent predictors of inferior 5-year overall survival, while AS histology and T2 invasiveness were predictors of inferior 5-year event-free survival. AS histology was the most important negative prognostic factor for overall survival and event-free survival. Completeness of primary tumor excision was a good prognostic factor for survival in univariate, but not multivariate, analysis. Local therapy (radiotherapy and delayed surgery) were provided to the minority of patients (28% and 38%, respectively) late in the course of disease (after a mean of 9 and 6 months, respectively) and did not prevent local relapses. Response to systemic treatment was poor (44%) and did not prevent local and distant relapses. The clinical course and outcome in childhood epithelioid HE seems to be similar to intravascular tumors and less aggressive than AS. RTX and delayed surgery should be performed more frequently and earlier in the disease course. An urgent need for modification of systemic therapy is needed because of the development of many metastatic and/or combined relapses and poor response to classic chemotherapy. The problem of effective therapy for childhood AS is the most appaling: 13 of 14 patients died of progression despite multimodal treatment.

The study was to determine clinical utility of serum soluble interleukin (IL)-2 receptor (sIL-2Ralpha), beta(2)-microglobulin (beta(2)-M), lactate dehydrogenase (LDH) and erythrocyte sedimentation rate (ESR) as markers of diagnosis, prognosis and monitoring of response to therapy in childhood Hodgkin's lymphoma (HL). The markers were measured prospectively before treatment and in complete remission (CR) during and after therapy in 30 children with HL (F/M:19/11; median age: 11.3 years) and once in 50 healthy children (F/M: 24/26; median age: 8.7 years). Median pretreatment levels of all analysed markers were significantly higher than in healthy controls. Increased pretreatment sIL-2Ralpha, LDH and ESR correlated with bulky disease; sIL-2Ralpha, beta(2)-M and ESR with presence of B symptoms and sIL-2Ralpha and LDH with advanced HL stages. There was a correlation between sIL-2Ralpha and LDH and between beta(2)-M and ESR. The levels and rates of elevated markers reflected well the response to chemotherapy, decreasing significantly when patients achieved CR and further on with therapy continuation. Since all patients survived thus the markers' value to predict the outcome was not established. Serum sIL-2Ralpha, beta(2)-M, LDH and ESR may act as markers for diagnostics and used in monitoring of therapy effectiveness in childhood HL. The markers were also increased in subgroups of patients with unfavourable clinical features; however, small sample size of the study did not allow to draw conclusion on their prognostic roles. We were also not able to establish the influence of markers on event free survival and overall survival because all children survived independent of initial clinical characteristics and pretreatment levels of sIL-2Ralpha, beta(2)-M, LDH and ESR.

Cancer growth and development is associated with the stimulation of the innate immune system, including enhanced interleukin 2 receptor (IL-2R) expression in immune cells and its shedding into the circulation in a soluble form of sIL-2Ralpha. In most haematological malignancies, including different types of leukaemias and lymphomas, sIL-2Ralpha has been found to be released directly from the surface of neoplastic cells thus reflecting the tumour bulk, turnover and activity. Several studies have proved that not only lymphoid cancer cells, but also some non-lymphoid cancer cells, express IL-2R on their surface. They include malignant melanoma and carcinomas of the kidney, head and neck, oesophagus and lung. It is suggested that in most malignant solid tumours, elevated levels of sIL-2Ralpha are likely to be the product of normal peripheral mononuclear cells activated in response to the neoplasm's growth or that they are released from activated lymphoid cells infiltrating neoplastic tissues. This latter hypothesis has been proved by discovering the high expression of CD25 on the cell surface of most of these cells. Although the precise source and biological role of sIL-2Ralpha has not been clarified definitively, pretreatment serum levels of sIL-2Ralpha have been shown to reflect the activity, advancement and biological aggressiveness of many types of cancer in adults and children as well as to correlate with prognosis and overall survival. The possibility of enriching the diagnostic tools of oncologists with a new biochemical marker of activity of neoplasms resulted in numerous studies and reports concerning the clinical usefulness of sIL-2Ralpha measurements in adult and, less frequently, in paediatric malignancies. This article presents the actual knowledge concerning the structure, source and biological function of sIL-2Ralpha in patients with haematological and non-haematological malignancies. The authors review the published data on clinical applicability of soluble IL-2Ralpha determination in terms of diagnostics, prognosis and treatment monitoring of particular types of malignant disorders both in adults and in children. They also provide an insight into the clinical usefulness of sLL-2Ralpha-blocking antibodies in patients with cancer, and in those who reject organ transplants, develop graft-versus-host disease after allogeneic bone marrow transplantation and are affected with autoimmune disorders.

Materials & methods: Polymorphic variants of IL-2 gene (-330 T/G and +166 G/T), IL-10 gene (-1082 G/A and -819 C/T) and serum cytokines concentrations in the group of 179 patients with BCC and 173 controls were analyzed. Results: The presence of the IL-2 -330 GG genotype or IL-10 -1082 GA increased the risk of BCC (OR 3.68) (OR 3.07). IL-10 -1082 AA or GA and IL-2 -330 GG genotype increased the risk of BCC (OR 9.63). IL-2 serum levels were significantly lower (p < 0.0004) in BCC patients while IL-10 concentration was significantly higher (p < 0.00001). Conclusion: The polymorphisms in IL-2 and IL-10 genes may contribute to BCC susceptibility and influence the clinical course of BCC in polish population.

Protocols for pediatric germ cell tumors (GCT) allow for chemotherapy (CHT) initiation without histological diagnosis, based on typical clinical and radiological picture and increased alphafetoprotein (AFP) or beta-human chorionic gonadotropin serum levels. Such strategy may result in misdiagnoses in rare cases. We present two patients with abdominal tumors and high serum AFP levels, diagnosed as GCT. In both, no tumor shrinkage and increasing AFP was observed after first cycles of multidrug CHT for pediatric GCT. Histological examination of biopsied tumor tissues revealed metastatic cholangiocarcinoma in patient 1 and pancreatoblastoma in patient 2, which implicated immediate change of therapy. Presented cases support the necessity to consider the tumor biopsy when patients diagnosed with GCT based on typical clinical presentation and elevated AFP do not respond to CHT with AFP decrease and tumor size reduction.

S -citalopram (escitalopram) mediates the serotonin reuptake inhibitory effect of the racemate, R , S -citalopram. The effect of escitalopram (0.5–3.9 mg/kg) was investigated in a rat conditioned fear stress model of anxiety and compared to the effects of R -citalopram (1.0–7.8 mg/kg), R , S -citalopram (4.0 and 8.0 mg/kg), and escitalopram (2.0 mg/kg)+ R -citalopram (7.8 mg/kg). Diazepam (0.95 mg/kg) and buspirone (4.6 mg/kg) were included as positive controls. During an acquisition session, rats were allowed to freely explore a novel cage for 9 min. During that time, they received two inescapable footshocks through an electrifiable grid floor. Groups of nonshocked control rats were run in parallel. During an expression session on the next day, rats were treated with drug or vehicle 30 min before they were reintroduced into the test cage for a 9-min period this time without receiving footshocks and the total distance travelled was recorded. The distance travelled by vehicle-treated rats was markedly suppressed compared to a vehicle-treated group of nonshocked controls. Escitalopram produced a dose-dependent inhibition of the conditioned suppression of exploratory behaviour (minimal effective dose 1.0 mg/kg). Interestingly R , S -citalopram 4.0 and 8.0 mg/kg produced significantly smaller effect than escitalopram 2.0 and 4.0 mg/kg, receptively. R -citalopram, 7.8 mg/kg, produced a significant effect. However, in spite of this, R -citalopram (7.8 mg/kg) significantly inhibited the effect of escitalopram (2.0 mg/kg). The activity in drug-treated nonshocked groups was similar to the vehicle-treated group, except for the buspirone-treated group where a significant reduction was observed. The finding that R -citalopram inhibits the effect of escitalopram may be relevant to the improved clinical efficacy seen with escitalopram compared to R , S -citalopram in the treatment of anxiety and depression.

Background Thymomas and thymic carcinomas belong to a group of thymic epithelial tumours arising from the anterior mediastinum and, are extremely rare in children in which no therapeutic guidelines have been established. The aim is to describe paediatric characteristics of these tumours and give some therapeutic indications. Methods Retrospective analysis of clinical data and therapeutic characteristics of paediatric patients less than 18 years with thymic tumours treated between 2000 and 2012 registered in the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) database of the cooperating national rare paediatric tumour working groups from France, Italy, Germany and Poland. Results Sixteen children with thymoma, median age 11 years and 20 patients with thymic carcinoma, median age 14 years were enrolled into study. At diagnosis complete primary resection was possible in 11 patients with thymoma and one with thymic carcinoma; resection with microscopic residue was performed in three cases and incomplete resection with macroscopic residue in four patients. Chemotherapy with various regimens was administered to 22 children; 17 of them as neoadjuvant chemotherapy. Eight patients with thymic carcinoma received additional radiotherapy. Seventeen children died (15 thymic carcinoma, two thymoma). Five-year overall survival for patients with thymic carcinoma is 21.0 ± 10.0%. Conclusions This study confirms the possibility to perform European retrospective analysis even in very rare paediatric tumours. Thymic carcinoma is associated with paediatric patients to give a very poor prognosis independently despite multimodal management. Multidisciplinary, multicenter approach and collaboration with adults’ physician are necessary in order to propose homogenous guidelines.

Objective To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification. Patients Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies ( n =23), French TGM protocols ( n =10), Italian Rare Tumour Project (TREP) registry ( n =6), and the Polish Pediatric Rare Tumour Study group ( n =5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO). Results Median age was 13.9 (0.5–17.4) years. All patients underwent resection by tumour enucleation ( n =8), ovariectomy ( n =17), adenectomy isolated ( n =18) or with hysterectomy ( n =1). FIGO-stage: Ia 24pts., Ic 17pts., II/III 3pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic–III), eight relapsed, and five patients died. Eleven patients were initially treated with two to sixcycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62months, event-free survival is 0.70±0.07, relapse-free survival 0.81±0.06 and overall survival 0.87±0.05. Conclusions Prognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated.

Background Pleuropulmonary blastoma (PPB) is an aggressive embryonal malignancy presenting in early childhood, presumably arising from pleuropulmonary mesenchyme. The European Cooperative Study Group for Paediatric Rare Tumours (EXPeRT) analysed its data on this tumour. Methods This analysis concerns patients aged 0–17 years with histologically-confirmed PPB registered up to 2008 in national databases in Italy, France and the United Kingdom and Poland. Lesions were classified as type I, II or III according to Dehner’s classification. Findings Sixty-five patients were considered (13 type I, 24 type II and 28 type III). Most tumours were large (91% >5 cm) and invaded the parietal pleura (29), mediastinum (10), major vessels (four) or pericardium (three). Regional nodes were involved in two cases, and three had metastases. The median follow-up was 5 years (0.6–22). For type I patients, 5-year progression free survival (PFS) was 83.3% and overall survival 91.7%; six patients received no further treatment after surgery, but two relapsed. All type II/III PPB had chemotherapy (CT) and their 5-year PFS was 42.9% (27.7–57.2). On univariate analysis, favourable prognostic factors were: complete tumour resection at diagnosis ( p = 0.008); and absence of invasiveness ( p = 0.02); for type II/III tumours, type of CT was also a significant factor (patients given doxorubicin fared better, with a 5-year PFS of 70% versus 31.3% [ p = 0.01]). Interpretations Type I PPB patients’ outcome was satisfactory. Complete resection at diagnosis seems important but rarely feasible for type II/III tumours, who benefited from doxorubicin-containing CT regimens. These results will inform the EXPeRT group’s PPB treatment guidelines.

INTRODUCTION Pre-treatment serum IL-10/IL-12 balance has been recently found deregulated in childhood soft tissue sarcomas (STS). Its role in STS monitoring and assessment of response to therapy is unknown. OBJECTIVE To establish whether serum IL-10 and IL-12 levels and their reciprocal ratios reflect childhood STS course and actual activity and whether G-CSF therapy and central vein catheter (CVC)-related sepsis influence the interleukins levels. MATERIALS AND METHODS ELISA determinations of serum interleukins were performed before treatment, in remission without complications (CR), at relapse and after treatment in 59 STS patients and during G-CSF administration and CVC-related sepsis (in 18) and also in 30 healthy controls. RESULTS In CR IL-10 declined and IL-12 increased as compared to pretreatment levels; in relapse IL-10 rose and IL-12 decreased significantly as compared to levels in CR. Also rates of IL-10, IL-12, and IL-10/IL-12 ratios recently estimated by us as of prognostic significance reflected well the STS course. During G-CSF therapy and CVC-related sepsis, IL-10 increased and IL-12 decreased significantly from levels in CR without complications. IL-10 levels and rates of IL-10 ≥ 11 pg/ml in sepsis could falsely suggest relapse. However, IL-12 levels, rates of IL-12 ≤ 60 pg/ml and/or simultaneous determination of both interleukins differed significantly from levels at relapse. CONCLUSION Serial determinations of serum IL-10 and IL-12 reflected well the course of STS in children and enabled remission and relapse phases to be distinguished. To avoid G-CSF and sepsis influence, IL-12 and IL-10/IL-12 ratio and not IL-10 alone should be analysed.

Context: The roles of interleukin 10 (IL-10) and IL-12 in regulation of cancer growth and Th1/Th2 immune responses towards cancer are unclear.Objective: To establish the prognostic significance of serum IL-10 and IL-12 in paediatric soft tissue sarcomas (STS).Materials and methods: ELISA determinations of cytokines were performed as pre-treatment in 59 children with STS and 30 healthy controls.Results: Elevated IL-10 and decreased IL-12 serum levels correlated with advanced disease, poor response to chemotherapy and poor outcome. IL-10 ≥ 9.5 pg/ml, IL-12 ≤ 65 pg/ml and lymph nodes involvement independently predicted poor overall survival (OS) in multivariate Cox analysis.Conclusion: Serum IL-10/IL-12 balance determination may facilitate to assess risk groups and prognosis in childhood STS.

The low incidence and the heterogeneity of very rare tumors (VRTs) demand for international cooperation. In 2008, EXPeRT (European Cooperative Study Group for Pediatric Rare Tumors) was founded by national groups from Italy, France, United Kingdom, Poland and Germany. The first aims of EXPeRT were to agree on a uniform definition of VRTs and to develop the currently most relevant scientific questions. Current initiatives include international data exchange, retrospective and prospective studies of specific entities, and the development of harmonized and internationally recognized guidelines. Moreover, EXPeRT established a network for expert consultation to assist in clinical decision in VRTs.

Pancreatoblastoma is a very rare malignant tumour typically occurring in the early years of life. Due to its rarity, standardised diagnostic and therapeutic guidelines are not available for pancreatoblastoma.The newborn cooperative group denominated EXPeRT - European cooperative study group for paediatric rare tumours - combined in a joint analysis of all cases registered between 2000 and 2009 by the national groups of Italy, France, United Kingdom, Poland and Germany.Twenty patients18years old (median age 4years) were analysed: nine had distant metastases at diagnosis. Seventeen patients had tumour resection, at initial or delayed surgery. Eighteen received chemotherapy (response rate 73%), seven received radiotherapy. For the whole series, 5-year event-free survival and overall survival were 58.8% and 79.4%, respectively. Outcome did not correlate with tumour site and size, but was strongly influenced by the feasibility of tumour complete resection.This international study confirms the rarity of the disease, the critical role of surgical resection both as therapy and as a prognostic variable, and the potential efficacy of chemotherapy. The adoption of an intensive multidisciplinary approach is required, as well as the referral to highly experienced centres. Further international cooperation is needed to collect larger series and stimulate biological studies to improve our understanding of the biology and the natural history of PBL.

Background: Pediatric hemangiopericytoma (HPC) is an extremely rare vascular tumor with little data available on its clinical course and management. Methods: Fourteen children with HPC registered in Polish Pediatric Rare Tumors and Polish Pediatric Soft-tissue Sarcomas Studies between 1992 and 2002 are reported. Results: Seven patients (F/M: 5/2, age 2–10 months) had infantile HPC, four of whom had primary tumors affecting superficial tissues of the trunk and upper limbs. No child had initial nodal or organ metastases. Primary excision (PE) was performed only in three patients with superficial lesions. They received no supplemental treatment. The remaining four children responded well to chemotherapy (CHT), entering complete remission after CHT alone (n= 2) or after delayed resection (n= 2). No relapses occurred and all patients were alive 48–146 months after treatment. Seven patients (F/M: 2/5, age 3.2–16.5 years) had adult-type HPC, five of whom had tumors localized in superficial tissues of the lower limbs or head/neck. All patients presented with locally advanced disease. PE was performed in five children (complete in four); all patients were alive at follow up of 40–127 months. Three patients died of recurrence after incomplete PE despite supplemental chemo- and radiotherapy. Conclusions: Complete surgical excision remains the mainstay of treatment for both HPC types. In unresectable adult-type HPC adjuvant chemo- and radiotherapy should be administered in macro- and microscopic tumor residues, but the prognosis is poor despite supplemental treatment. High chemo-responsiveness of infantile-type HPC produces a favorable outcome even in cases of unresectable, life-threatening tumors.

To establish the clinical utility of serum soluble IL-2 receptor (sIL-2R alpha), lactate dehydrogenase (LDH) [corrected] and B2-microglobulin [corrected] (B2-M) as markers for diagnosis, prognosis and treatment monitoring in childhood soft tissue sarcomas (STS).The markers[corrected] were measured prospectively before treatment, in complete remission (CR) during and after therapy and at relapse [corrected] in 35 children with STS and in 50 healthy children [corrected] (once).Serum sIL-2R alpha and LDH [corrected] correlated with age thus they were [corrected] presented as multiplications [corrected] of the upper normal ranges [corrected] for age. Pre-treatment levels [corrected] of sIL-2R alpha and LDH [corrected] but not of B2-M exceeded significantly those of controls. [corrected] Elevated [corrected] sIL-2R alpha levels correlated with more [corrected] advanced stages, poor-risk histology and poor response to chemotherapy, higher LDH with incomplete primary tumour [corrected] resection and increased B2-M with poor-risk histology. [corrected] Patients' age10 years, male gender and unfavourable tumour localisation were not accompanied by the markers' elevation. [corrected] None of the markers predicted EFS and OS. [corrected] Good response to chemotherapy was paralleled by significant decline of sIL-2R alpha and LDH pre-treatment levels while relapse--by sIL-2R alpha and LDH increase to values similar to those at diagnosis. [corrected] Monitoring of B2-M did not reflect the disease course. [corrected]sIL-2R alpha and LDH were [corrected] proven to be promising markers [corrected] for diagnosis and treatment monitoring in children with STS. The markers [corrected] correlated also with some [corrected] important prognostic clinico-pathological factors for childhood [corrected] STS; however, they [corrected] failed to predict EFS and OS. Measurements of serum [corrected] B2-M were shown [corrected] to have no clinical value in the diagnostics, prognostics and treatment monitoring in paediatric STS.

Objectives Deregulated serum IL-10, IL-12 and their reciprocal balance have been stated in malignancies of adults. In children with cancer the issue has not been investigated so far. Design and methods To determine the diagnostic and prognostic roles of pre-treatment serum levels of IL-10 (Th2 cytokine), IL-12 (Th1) and their ratios (measured by the IL-10 and IL-12p70 ELISA kits; Endogen) in 91 children with soft tissue sarcomas (STS), Hodgkin's lymphomas (HL) and acute lymphoblastic leukemias (ALL). Results Median IL-10 and IL-12 levels were significantly higher in cancer patients than in healthy controls. Increased IL-10 indicated presence of general symptoms in HL and high risk group in ALL. Elevated IL-10 and IL-10/IL-12 ratios and decreased IL-12 correlated with poor-risk histology in STS, poor response to therapy, relapse and death from cancer. Multivariate analysis identified IL-10/IL-12 ratio > 0.14 and IL-12 Conclusion Pre-treatment serum levels of IL-10, IL-12 and IL-10/IL-12 balance in children with STS, HL and ALL may be of value as additional prognostic tools to predict the response to therapy and probability of EFS and OS.

Malignant high-grade gliomas are the most common secondary neoplasms in children cured of acute lymphoblastic leukaemia (ALL). Although many predisposing factors exist (including systemic or intrathecal chemotherapy, young age, brain infiltration and genetic predispositions), cranial irradiation appears to be the strongest one. Three cases of secondary high-grade gliomas (two multiform glioblastomas, grade IV; one anaplastic astrocytoma, grade III) developed in ALL survivors (F–M, 1:2) 3 to 6.3 years after stopping ALL therapy according to BFM-90 trial. All tumours were supratentorial, contrast-enhancing, space-occupying, highly advanced and aggressive. Possible risk factors and current therapeutic options for paediatric ALL and malignant gliomas are reviewed and discussed. Prognosis in secondary malignant gliomas in children is poor (overall survival of 5, 10 and 19 months) despite intense therapy. Thus, protocols for paediatric ALL reduce prophylactic cranial irradiation in favour of intrathecal and intravenous high-dose MTX. Nevertheless, ALL survivors must undergo systematic, long-term surveillance for early detection of intracranial neoplasms.

THE AIM of the study was to evaluate the incidence of pulmonary complications in children cured from Hodgkin's disease (HD).42 children with HD were treated in the Department of Paediatrics, Haematology, Oncology and Endocrinology, Medical University of Gdansk, between 1994 and 2004. Stages of HD: II--26 children, III--10, IV--6; general symptoms (group B) were present in 50% of patients. Mediastinal involvement was found in 33 children, lung parenchyma infiltration in seven and bronchi involvement in one. In 1/3 of these patients the localization of HD within the chest was massive and symptomatic with signs of the superior caval vein symptoms, cough, dyspnea and cardiac tamponade. The treatment was conducted according to the schemes of the Polish Paediatric Leukaemia /Lymphoma Study Group. Eleven patients required therapy modification including six, in whom the intense line II chemotherapy Salvage 95 was introduced. 29 patients received chest irradiation with doses between J 75 and 36.5 Gy. Pulmonary function was evaluated from the results of clinical examination, 1 chest radiography (CXR), computed tomography, spirometry and lung scintigraphy.Pulmonary complications occurring as fatigue and diminished physical effort tolerance was observed in only two children. Some of the remaining 40 patients demonstrated asymptomatic abnormalities in the analysed tests. Abnormalities in CXR (upper mediastinal fibrosis, postoperational changes within the diaphragm and pneumonitis) were found in six children, minor ventilation problems in spirometry--in 12 and decreased lung perfusion in five. The scintigraphic signs of lung embolisation were not observed in our material. Most of the pulmonary complications occurred in children with enlarged lymph notes located within the chest, especially these with bulky disease presenting with cardio-pulmonary symptoms. In this group of patients the chest irradiation was performed in all except four children, three patients were also administered aggressive salvage chemotherapy.The pulmonary complications in children after completed therapy of HD are not common and mainly asymptomatic and occur predominantly in patients with massive mediastinal and/or lung involvement at diagnosis. The issue needs further evaluation of a more numerous group of HD survivors and a longer follow-up.

Patients with neurofibromatosis type 1 (NF1) are predisposed to developing soft tissue sarcomas (STS). We report on four cases of STS diagnosed in locally advanced, unresectable stages in children with NF1 (three girls, one boy; age = 8 months–14 years). All patients received protocols for STS: Cooperative Weichteilsarkomstudie 91, 96 and 2002. One patient with limb rhabdomyosarcoma entered complete remission but developed late metastatic relapse and died of progression despite complete excision and autologous bone marrow transplantation. The other patient with bladder rhabdomyosarcoma died of neutropenia-related sepsis without remission. Patients with malignant peripheral nerve sheet tumour and malignant triton tumour located in the pelvis did not respond to therapy. One of them died of disease progression, while the other is disease-free 6 years post-therapy after mutilating tumour resection. STS in NF1 seem to display poor prognosis in spite of combined therapy; thus, children with NF1 should remain under detailed control of the oncologist.

Lokalizacja nowotworu w obrebie glowy i szyi sprawia, ze wczesne rozpoznanie choroby jest trudne nawet dla doświadczonego lekarza. Powodem są: niecharakterystyczne wstepne objawy guza; niedostepnośc w badaniu tych regionow. Nowotworami litymi mogącymi lokalizowac sie w tej okolicy u dzieci są: miesaki prązkowanokomorkowe oraz raki. Leczenie obejmuje chemioterapie, resekcje chirurgiczną oraz radioterapie. Material i metoda Badaniem objeto 25 pacjentow leczonych z powodu nowotworow litych pierwotnie umiejscowionych w obrebie glowy i szyi w latach 1992–2002. Przeanalizowano objawy poprzedzające rozpoznanie i dlugośc ich trwania, typ histopatologiczny, stadium zaawansowania, wyniki terapeutyczne. Wyniki Plec: 13 chlopcow, 12 dziewczynek. Wiek: 2 do 17 lat. Okres od wstepnych objawow do rozpoznania: 2 do 24 miesiecy. Objawy kliniczne zglaszane: przedluzający sie ropny katar, krwawienie z nosa, porazenie nerwu twarzowego, bol ucha, szczekościsk, gorączka, spadek masy ciala. Wyniki badania patomorfologicznego: miesak prązkowanokomorkowy – 15 pacjentow, leimyosarcoma – 1, guz Tritona – 1, nabloniak chlonny – 6, cylindroma – 1 pacjent, acinic cell carcinoma – 1 pacjent. Przerzuty: CUN – 2 pacjentow, wezly chlonne szyjne – 10 pacjentow. Leczenie: wg programow przewidzianych dla danego typu nowotworu. Wyniki leczenia: calkowita remisja – 12 pacjentow (7 pacjentow z RMS, 3 z nabloniakiem chlonnym, 2 z acinic cell carcinoma); w trakcie leczenia – 2 pacjentow (1 pacjent z RMS i 1 z nabloniakiem chlonnym); w trackie leczenia pierwszej wznowy – 4 pacjentow (3 z RMS i 1 z nabloniakiem chlonnym); zgon – 7 pacjentow (4 pacjentow z RMS i 1 z guzem Tritona, 1 z nabloniakiem chlonnym, 1 z leimyosarcoma). Wnioski 1) Brak dostepności okolicy glowy i szyi, bliskośc OUN, niemoznośc resekcji z marginesem tkanek zdrowych oraz wczesne przerzuty/wznowy powodują, ze mimo intensywnego leczenia efekty terapeutyczne nowotworow tej okolicy są niezadawalające. 2) Lekarze podstawowej opieki zdrowotnej powinni w przypadku stwierdzenia niepokojących objawow bądz przedluzających sie infekcji przebiegających z powiekszeniem wezlow chlonnych szyjnych jak najszybciej kierowac pacjenta do ośrodka specjalistycznego.