Search

Background: Two principal approaches to Wilms tumor (WT) treatment are immediate surgery (IS) and preoperative chemotherapy (PCT), and both treatments use the risk-adapted approach that includes histological subclassification of the tumor, combined with additional prognostic factors. In the UKW3 trial, these two approaches were compared. The aim of the present study was to compare histological features between the two groups, to assess the impact of PCT on distribution of histological subtyping and staging and to evaluate whether PCT resulted in more staging discrepancies between local and central pathology review (CPR)., Materials and Methods: The cases were identified from the UKW3 trial database. The criteria for inclusion in the study were unilateral, nonmetastatic, nonanaplastic WTs, and submitted for CPR with an adequate number of slides. They were subclassified according to the NWTS and later the SIOP 9301 criteria., Results: There were 244 WTs in the IS and 182 in the PCT group subclassified as follows: blastemal 86 (35%) vs 9 (5%), epithelial 34 (14%) vs 12 (7%), stromal 12 (5%) vs 25 (14%), mixed 112 (46%) vs 45 (25%), respectively, plus 40% regressive and 10% completely necrotic WTs in the PCT group. The differences between the two groups for blastemal and mixed types were statistically significant. In the PCT group, there was a significant decrease in stage III tumors. The discrepancies in staging between local and CPR were not significant., Conclusion: PCT significantly altered histological features and typing of WTs. It resulted in fewer stage III tumors, and staging discrepancies were equally represented in both groups., (© 2018 Wiley Periodicals, Inc.)

Testicular germ cell tumours (TGCTs) are the most frequent malignancy and cause of death from solid tumours in the 20- to 40-year age group. Although most cases show sensitivity to cis-platinum-based chemotherapy, this is associated with long-term toxicities and chemo-resistance. Roles for receptor tyrosine kinases other than KIT are largely unknown in TGCT. We therefore conducted a phosphoproteomic screen and identified the insulin growth factor receptor-1 (IGF1R) as both highly expressed and activated in TGCT cell lines representing the nonseminomatous subtype. IGF1R was also frequently expressed in tumour samples from patients with nonseminomas. Functional analysis of cell line models showed that long-term shRNA-mediated IGF1R silencing leads to apoptosis and complete ablation of nonseminoma cells with active IGF1R signalling. Cell lines with high levels of IGF1R activity also showed reduced AKT signalling in response to decreased IGF1R expression as well as sensitivity to the small-molecule IGF1R inhibitor NVP-AEW541. These results were in contrast to those in the seminoma cell line TCAM2 that lacked IGF1R signalling via AKT and was one of the two cell lines least sensitive to the IGF1R inhibitor. The dependence on IGF1R activity in the majority of nonseminomas parallels the known role of IGF signalling in the proliferation, migration, and survival of primordial germ cells, the putative cell of origin for TGCT. Upregulation of IGF1R expression and signalling was also found to contribute to acquired cisplatin resistance in an in vitro nonseminoma model, providing a rationale for targeting IGF1R in cisplatin-resistant disease. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland., (© 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH) in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA) are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT); current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information., Patients and Methods: We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling., Results: From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26-16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36-31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes., Conclusion: This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker.

Inflammatory myofibroblastic tumor is a neoplasm of intermediate biological potential, a marked inflammatory component, and characteristic genetic changes. Once it was identified as an independent nosological entity from a rather heterogeneous group of inflammatory pseudotumors. This paper describes a case of inflammatory myofibroblastic tumor of the chest in a child, by discussing the criteria for differential diagnosis in the use of up-to-date radiology techniques. When thoracic neoplasms are detected, it is necessary to determine their site and the most likely origin organ as exactly as possible and to assess the X-ray pattern of the pathological process. By applying the state-of-the-art radiodiagnostic techniques, the clarification of the pattern of the disease makes it possible to choose an optimal treatment policy and a surgical procedure and scope, to avoid anesthesia overload, and to decrease the probability of resurgery. Our observation is to demonstrate possible problems in the diagnosis of inflammatory myofibroblastic tumor of the lung in childhood and to recall again the algorithm of radiological approaches to detecting mediastinal and lung masses.

Wilms tumor (WT) with diffuse anaplasia has an unfavorable prognosis and is often (>70%) associated with mutations in the TP53 gene. Although most WTs are unilateral, 5-10% are bilateral, and they are almost always present with nephrogenic rests. The latter are considered a precursor of WT. Two cases of bilateral WTs with nephroblastomatosis, in which anaplastic changes were detected over a period of time, were analyzed using clinical, radiological, histopathological, and molecular-genetic data. TP53 was analyzed by direct sequencing of its full coding sequence and intron-exon boundaries in 11 fragments. DNA was extracted from paraffin-embedded or frozen specimens. High-resolution genomic copy number profiling was carried out by UCL Genomics on the Affymetrix Human Mapping 250K Nsp or Genome-Wide Human SNP Array 6.0 platform. Both cases demonstrated a strong association between the appearance of anaplastic clones and TP53 mutations. Synchronous ganglioneuroma was diagnosed in one case. Our cases are unique as they represent a long disease history and demonstrate the difficulties in managing rare cases of bilateral WT with anaplasia. These cases also emphasize the practical importance of modern molecular-genetic techniques and their clinical application. Moreover, they highlight the issue of the adequate sampling needed in order to gather comprehensive, efficient, and sufficient information about genetic events in a single tumor.

The batch fermentation process of sugar beet processing intermediates by free yeast cells is the most widely used method in the Autonomous Province of Vojvodina for producing ethanol as fuel. In this study a process and cost model was developed for producing ethanol from raw juice. The model can be used to calculate capital investment costs, unit production costs and operating costs for a plant producing 44 million l of 99.6% pure ethanol annually. In the sensitivity analysis the influence of sugar beet and yeast price, as well as the influence of recycled biomass on process economics, ethanol production costs and project feasibility was examined. The results of this study clearly demonstrate that the raw material costs have a significant influence on the expenses for producing ethanol. Also, the optimal percentage of recycled biomass turned out to be in the range from 50% to 70%., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Wilms tumor is the most common renal tumor of childhood. However, other epithelial, mesenchymal, and neuroectodermal neoplasms may also arise in the kidney during childhood, several of which show specific age distributions; in the 1st year of life, mesoblastic nephroma and rhabdoid tumor are more common, whereas renal cell carcinoma, primitive neuroectodermal tumor, and anaplastic Wilms tumors are relatively more frequent in older children and adolescents. The aim of this study is to describe the spectrum of renal tumors in children aged 10-16 years using data from 1492 patients registered in the UK Wilms Tumour 3 Trial (1991-2001) and International Society of Paediatric Oncology Wilms Tumour Trial 2001 (2002-2008) clinical trials of renal tumors in childhood. There were 67 (4.6%) tumors in children aged 10-16 years: 50 Wilms tumors (74.6%), 10 (14.9%) renal cell carcinomas, 3 (4.5%) renal medullary carcinomas, 2 (3%) primitive neuroectodermal tumors, 1 clear cell sarcoma of kidney, and 1 desmoplastic small round cell tumor. Fourteen percent of the Wilms tumors in this age group had diffuse anaplasia. Among the 10 renal cell carcinomas, 4 were associated with t(Xp-11.2), 3 were of papillary type II, 1 was papillary type I, 1 was clear cell type, and 1 was unclassified. Five-year overall survival for Wilms tumor was 63% (43% for anaplastic tumors), significantly lower than reported overall survival for all pediatric Wilms tumors. Only 40% of patients with renal cell carcinoma survived, and all patients with other tumors died.

Neonatal interstitial emphysema (IE) may develop as a complication of the respiratory distress syndrome. IE is classified as acute and persistent and as diffuse and local forms. The differential diagnosis of persistent IE and congenital cystic malformations from clinical and imaging data may present problems. The histological pattern of persistent IE has specific features that permit the morphological diagnosis of this condition.

There may be a number of tumors made up by small round blue cells in the kidneys of children. One of them is primitive neuroectodermal tumor (PNET). The differences in therapeutic approaches determine the need to establish an accurate diagnosis. The differential diagnosis of PNET and the blastemal component of Wilms tumor can be difficult due to the similar histological pattern. There is a need for a close analysis of morphological manifestations, by keeping in mind the age of patients, and supplementary studies. A strong CD99 membrane expression and nuclear FLI1 expression in tumor cells are the signs of PNET. Reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization can determine PNET-specific translocations [t(11;22)(q24;q12), by involving the EWS gene.

A morphological study of renal tumors in children requires the accurate diagnosis of the histological type and stage of a tumor and the evaluation of its risk in accordance with the SIOP protocol standards. Pathological findings may provide the most adequate therapeutic approach in every specific case. It is necessary to correctly analyze the results of studies and to elaborate the most effective and adequate treatment

Solitary orbital fibrous tumor was diagnosed in a 12-year old boy admitted to hospital for right-sided exophthalmos. MRI revealed orbital mass and surgical resection was performed. Histologically the tumor was composed of round or spindle cells with a lot of multinucleate giant cells and pseudovascular spaces. The neoplasm was regarded as a mixoid type of a solitary giant cell-rich fibrous tumor. Immunohistochemical analysis revealed coexpression of CD34, CD99, bcl-2, and CD99 (mic-2). The most important clinical, morphological, and immunohistochemical manifestations are presented in the paper. Major criteria for the differential diagnosis of solitary orbital fibrous tumor and the similar soft tissue tumors are discussed.

Solitary fibrous tumor is a rare neoplasm which may occur at any site although it is more frequent in the pleura, mediastinum and lung. The study used 4 cases of tumor localization in the pleura and orbit. Three cases presented as a "hemangiopericytic" variety of spindle cells; there were numerous giant cells in orbit tumor. Solitary fibrous tumor revealed enhanced expression of vimentin, CD34, bel-2 and CD99. Expression of S-100, desmine and non-striated muscle actin was found in few cells in some cases. Such features as large size (over 10 cm), necrosis, high cellularity, nuclear polymorphism and high mitotic index (more than 4 mitoses within 4 visual fields, at high magnification) were used as malignancy criteria:. Tumor histological pattern of "hemangiopericytic" variety could be reliably identified thanks to immunohistochemical procedure.

A 12 year old boy was admitted to the hospital with complaints of stomachache, weight loss, weakness. The first symptoms appeared 6 months ago after intake of the mixture of vinegar, soda and gasoline. The endoscopy showed polypoid mass in the angle of the stomach and malignancy was suspected. Partial resection of the stomach was performed and the boy was discharged from the hospital if satisfactory condition. Microscopic investigation detected spread of fibroblast-like cells containing lengthened nuclei with distinct nucleoli in some of them. There was prominent inflammatory reaction with the presence of neutrophils, macrophages, lymphocytes and many plasma cells. Immunohistochemical analysis showed positive reactions with smooth muscle actin and vimentin. The mass was considered to be an inflammatory pseudotumor. The fact that the lesion developed after the action of the aggressive fluid on the stomach wall permits to consider this event as a possible etiologic factor.

The highest amount of zinc (approximately 90%) is bound after 3 h of contact at low initial (total) concentrations of zinc in yeast broth, 2.0-16.0 g/l at 10-30 degrees C. The equilibrium between bound and free zinc ions is established after 6 h of contact time, independently on total zinc concentration in yeast milk. No bigger changes of content of zinc bound to yeast cells was determined at 10 degrees C and 30 degrees C. 40% of bound zinc in the equilibrium state is bound during the first 15 min of contact of zinc ions and yeast cells at all initial (total) zinc concentrations in yeast milk both at 10 degrees C and 30 degrees C. The KEKAM (Kolmogorov-Erofeev-Kozeeva-Avrami-Mampel) equation can be used for the description of kinetics of zinc biosorption by yeast cells, for the ranges of zinc concentration of 2.0-16.0 g/l at 30 degrees C (mean correlation coefficient 0.96) and 10.0-16.0 g/l at 10 degrees C (mean correlation coefficient 0.95).

The article touches upon problems of the improvement of transfusiological maintenance of surgical departments with new tendencies in the donor movement taken into account. Specific methods to gain this aim are proposed.

The results of polymerization chain reaction (PCR) and morphological study are compared. The presence of cytomegalovirus (CMV) DNA in the organs of dead children is demonstrated by PCR in 13 of 16 cases. In 3 of 13 cases structural changes typical for CMV infection were absent; slight symptoms of the damage produced by DNA-virus were present in 4 cases. The results indicate that there exist variants of CMV infection with a minimum manifestation of the infectious process. The presence of mutations in the CMV genome was revealed in 6 cases.

The results of examination of 87 children who died from a generalized cytomegalovirus infection in Elista (66 cases) in 1984-1985, 1988-89, and in Leningrad (21 cases) in 1988-89 are available. In the Elista material a considerable increase (from 21 to 66%) of severe forms of accidental transformation of thymus is observed in the second period comparing to the first one. The causes of a serious worsening of the immunological background remain unclear. Cytomegaly represented 3.85% of all dead children in the pathology department of the First Children Hospital of Leningrad. There was sialadenitis in 4 cases and generalized infection with involvement of the lungs, liver, kidneys, brain, myocardium, pancreas, adrenals in 17 cases. Cytomegaly was diagnosed in 3 of 5 cases of primary immunodeficiency. Diagnosis in some cases was confirmed by the DNA cytomegalovirus detection by means of PCR reaction.

The achievements of Soviet transfusiology in the period of the Great Patriotic War of 1941-1945 and of the Soviet medicine in the following years represent a basis for the successful development of Soviet transfusiology under modern conditions.

In experiments on animals and isolated livers from human cadavers an opportunity of using a direct ascending cholegraphy for roentgenological diagnosis of gunshot injuries of the liver was studied, rather demonstrative roentgenograms, photographs given in the paper being obtained.