• MeSH
• environmentální lékařství MeSH
• nemoci z povolání MeSH
• Publikační typ
• periodika MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• pracovní lékařství
• environmentální vědy

PURPOSE: To evaluate the impact of surgeon-assessed extent of primary tumor resection on local progression and survival in patients in the International Society of Pediatric Oncology Europe Neuroblastoma Group High-Risk Neuroblastoma 1 trial. PATIENTS AND METHODS: Patients recruited between 2002 and 2015 with stage 4 disease > 1 year or stage 4/4S with MYCN amplification < 1 year who had completed induction without progression, achieved response criteria for high-dose therapy (HDT), and had no resection before induction were included. Data were collected on the extent of primary tumor excision, severe operative complications, and outcome. RESULTS: A total of 1,531 patients were included (median observation time, 6.1 years). Surgeon-assessed extent of resection included complete macroscopic excision (CME) in 1,172 patients (77%) and incomplete macroscopic resection (IME) in 359 (23%). Surgical mortality was 7 (0.46%) of 1,531. Severe operative complications occurred in 142 patients (9.7%), and nephrectomy was performed in 124 (8.8%). Five-year event-free survival (EFS) ± SE (0.40 ± 0.01) and overall survival (OS; 0.45 ± 0.02) were significantly higher with CME compared with IME (5-year EFS, 0.33 ± 0.03; 5-year OS, 0.37 ± 0.03; P < .001 and P = .004). The cumulative incidence of local progression (CILP) was significantly lower after CME (0.17 ± 0.01) compared with IME (0.30 ± 0.02; P < .001). With immunotherapy, outcomes were still superior with CME versus IME (5-year EFS, 0.47 ± 0.02 v 0.39 ± 0.04; P = .038); CILP was 0.14 ± 0.01 after CME and 0.27 ± 0.03 after IME (P < .002). A hazard ratio of 1.3 for EFS associated with IME compared with CME was observed before and after the introduction of immunotherapy (P = .030 and P = .038). CONCLUSION: In patients with stage 4 high-risk neuroblastoma who have responded to induction therapy, CME of the primary tumor is associated with improved survival and local control after HDT, local radiotherapy (21 Gy), and immunotherapy.

• MeSH
• cytoredukční chirurgie škodlivé účinky   metody   statistika a číselné údaje   MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• multicentrické studie jako téma MeSH
• neuroblastom mortalita   patologie   chirurgie   terapie   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• proporcionální rizikové modely MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• staging nádorů MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Risk stratification is crucial to treatment decision-making in neuroblastoma. This study aimed to explore factors present at diagnosis affecting outcome in patients aged ≥18 months with metastatic neuroblastoma and to develop a simple risk score for prognostication. PROCEDURE: Data were derived from the European high-risk neuroblastoma 1 (HR-NBL1)/International Society for Paediatric Oncology European Neuroblastoma (SIOPEN) trial with analysis restricted to patients aged ≥18 months with metastatic disease and treated prior to the introduction of immunotherapy. Primary endpoint was 5-year event-free survival (EFS). Prognostic factors assessed were sex, age, tumour MYCN amplification (MNA) status, serum lactate dehydrogenase (LDH)/ferritin, primary tumour and metastatic sites. Factors significant in univariate analysis were incorporated into a multi-variable model and an additive scoring system developed based on estimated log-cumulative hazard ratios. RESULTS: The cohort included 1053 patients with median follow-up 5.5 years and EFS 27 ± 1%. In univariate analyses, age; serum LDH and ferritin; involvement of bone marrow, bone, liver or lung; and >1 metastatic system/compartment were associated with worse EFS. Tumour MNA was not associated with worse EFS. A multi-variable model and risk score incorporating age (>5 years, 2 points), serum LDH (>1250 U/L, 1 point) and number of metastatic systems (>1, 2 points) were developed. EFS was significantly correlated with risk score: EFS 52 ± 9% for score = 0 versus 6 ± 3% for score = 5 (P < 0.0001). CONCLUSIONS: A simple score can identify an "ultra-high risk" (UHR) cohort (score = 5) comprising 8% of patients with 5-year EFS <10%. These patients appear not to benefit from induction therapy and could potentially be directed earlier to alternative experimental therapies in future trials.

• MeSH
• dítě MeSH
• doba přežití bez progrese choroby MeSH
• ferritiny krev   MeSH
• Kaplanův-Meierův odhad MeSH
• klinické zkoušky jako téma MeSH
• kojenec MeSH
• L-laktátdehydrogenasa krev   MeSH
• lidé MeSH
• nádorové biomarkery analýza   MeSH
• neuroblastom mortalita   patologie   MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• protoonkogen n-myc genetika   MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The purpose of this study was to evaluate whether levels of neuroblastoma mRNAs in bone marrow and peripheral blood from stage M infants (≤12 months of age at diagnosis, MYCN amplified) and toddlers (between 12 and 18 months, any MYCN status) predict event-free survival (EFS). METHODS: Bone marrow aspirates and peripheral blood samples from 97 infants/toddlers enrolled in the European High-Risk Neuroblastoma trial were collected at diagnosis in PAXgene™ blood RNA tubes. Samples were analyzed by reverse transcription quantitative polymerase chain reaction according to standardized procedures. RESULTS: Bone marrow tyrosine hydroxylase (TH) or paired-like homeobox 2b (PHOX2B) levels in the highest tertile were associated with worse EFS; hazard ratios, adjusted for age and MYCN status, were 1.5 and 1.8 respectively. Expression of both TH and PHOX2B in the highest tertile predicted worse outcome (p = 0.015), and identified 20 (23%) infants/toddlers with 5-year EFS of 20% (95%CI: 4%-44%). Prognostic significance was maintained after adjusting for over-fitting bias (p = 0.038), age and MYCN status. In peripheral blood, PHOX2B levels in the highest tertile predicted a two-fold increased risk of an event (p = 0.032), and identified 23 (34%) infants/toddlers with 5-year EFS of 29% (95%CI: 12%-48%). Time-dependent receiver operating characteristic analysis confirmed the prognostic value of combined TH and PHOX2B in bone marrow and of PHOX2B in peripheral blood during the first year of follow-up. CONCLUSIONS: High levels of bone marrow TH and PHOX2B and of peripheral blood PHOX2B at diagnosis allow early identification of a group of high-risk infant and toddlers with neuroblastoma who may be candidates for alternative treatments. Integration with additional biomarkers, as well as validation in additional international trials is warranted.

• MeSH
• doba přežití bez progrese choroby MeSH
• homeodoménové proteiny analýza   biosyntéza   MeSH
• Kaplanův-Meierův odhad MeSH
• kojenec MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• nádorové biomarkery analýza   MeSH
• neuroblastom metabolismus   mortalita   MeSH
• novorozenec MeSH
• plocha pod křivkou MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• ROC křivka MeSH
• senzitivita a specificita MeSH
• transkripční faktory analýza   biosyntéza   MeSH
• tyrosin-3-monooxygenasa analýza   biosyntéza   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

Juxtaglomerular cell tumors (JGCTs) are rare tumors characterized by renin synthesis, hyperaldosteronism and hypertension. A curious immunohistochemical overlap between JGCT and gastrointestinal stromal tumor (GIST) including the expression of vimentin, CD34, CD117, alpha-smooth muscle actin was previously reported, prompting us to further investigate JGCT and its phenotypic and molecular genetic characteristics. Virtual karyotyping showed gain of chromosomes 3, 4, 10, 13, 17 and 18 in one JGCT, and fluorescence in situ hybridization (FISH) study confirmed this multiple gain pattern. Additionally, loss of chromosome 9 was observed in four of six cases analyzed with FISH. A whole genome expression analysis revealed 415 up-regulated (including renin, and CD117) and 325 down-regulated genes between the 2 cases. The study confirmed earlier reports on the gain of chromosomes 4 and 10, and provided further evidence of up-regulation of the genes located on these 2 chromosomes. For the first time our study indicated the importance of the loss of chromosome 9 and loss of expression of several tumor suppressor genes located on this chromosome as possible pathogenetic events important in development of JGCT.Copyright © 2013 Elsevier Inc. All rights reserved.

• MeSH
• beta-katenin MeSH
• cytoplazmatická granula MeSH
• dospělí MeSH
• imunohistochemie MeSH
• juxtaglomerulární aparát MeSH
• karyotypizace MeSH
• lidé MeSH
• mladý dospělý MeSH
• protoonkogenní proteiny c-kit MeSH
• renin MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

We present a cohort of 8 renal carcinomas that displayed a variable (5%-95% extent) light microscopic appearance of renal angiomyoadenomatous tumor/clear cell papillary renal cell carcinoma (RAT/CCPRCC) without fulfilling the criteria for these tumors. All but 1 case predominantly (75%-95% extent) showed histopathologic features of conventional clear cell renal cell carcinoma. In 5 of 7 cases with mostly conventional clear renal cell carcinoma (CRCC) morphology, a diagnosis of CRCC was supported by the molecular genetic findings (presence of von Hippel-Lindau tumor suppressor [VHL] mutation and/or VHL promoter methylation and/or loss of heterozygosity [LOH] for 3p). Of the other 2 cases with predominantly characteristic CRCC morphology, 1 tumor did not reveal any VHL mutation, VHL promoter methylation, or LOH for 3p, and both chromosomes 7 and 17 were disomic, whereas the other tumor displayed polysomy for chromosomes 7 and 17 and no VHL mutation, VHL promoter methylation, or LOH for 3p. One tumor was composed primarily (95%) of distinctly RAT/CCPRCC-like morphology, and this tumor harbored a VHL mutation and displayed polysomy for chromosomes 7 and 17. Of the 5 cases with both histomorphologic features and molecular genetic findings of CRCC, we detected significant immunoreactivity for alpha-methylacyl-CoA racemase in 2 cases and strong diffuse immunopositivity for cytokeratin 7 in 3 cases. Despite the combination of positivity for alpha-methylacyl-CoA racemase and cytokeratin 7 in 2 cases, there was nothing to suggest of the possibility of a conventional papillary renal cell carcinoma with a predominance of clear cells.Copyright © 2013 Elsevier Inc. All rights reserved.

• MeSH
• adenom * diagnostické zobrazování   MeSH
• angiomyom * diagnóza   MeSH
• chromozomální aberace MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• karcinom z renálních buněk * diagnóza   MeSH
• keratin-7 metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 17 MeSH
• lidské chromozomy, pár 7 MeSH
• mnohočetné primární nádory diagnóza   MeSH
• mutace MeSH
• nádorový supresorový protein VHL genetika   MeSH
• nádory ledvin * diagnóza   MeSH
• papilární karcinom * diagnóza   MeSH
• racemasy a epimerasy metabolismus   MeSH
• senioři MeSH
• von Hippelova-Lindauova nemoc MeSH
• ztráta heterozygozity MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

• MeSH
• diferenciální diagnóza MeSH
• gastrointestinální nemoci diagnóza   patologie   MeSH
• histologie MeSH
• lidé MeSH
• zánět diagnóza   MeSH
• Check Tag
• lidé MeSH

• MeSH
• acinární karcinom mortalita   patologie   sekundární   MeSH
• dítě MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• nádory slinných žláz metabolismus   mortalita   patologie   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

• MeSH
• aktiny metabolismus   MeSH
• chondroblastom metabolismus   patologie   ultrastruktura   MeSH
• chondrom metabolismus   MeSH
• chondrosarkom metabolismus   MeSH
• chrupavka metabolismus   patologie   ultrastruktura   MeSH
• elektronová mikroskopie MeSH
• imunohistochemie MeSH
• lidé MeSH
• Check Tag
• lidé MeSH

• MeSH
• chemie MeSH
• inhibitory enzymů chemie   metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• saponiny chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH