Omission of doxorubicin from the treatment of stage II-III, intermediate-risk Wilms' tumour (SIOP WT 2001): an open-label, non-inferiority, randomised controlled trial.

Background: Before this study started, the standard postoperative chemotherapy regimen for stage II-III Wilms' tumour pretreated with chemotherapy was to include doxorubicin. However, avoidance of doxorubicin-related cardiotoxicity effects is important to improve long-term outcomes for childhood cancers that have excellent prognosis. We aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumour when a newly defined high-risk blastemal subtype was excluded from randomisation.

Pulmonary alveolar proteinosis in children on La Réunion Island: a new inherited disorder?

Background: Pulmonary alveolar proteinosis (PAP) is very rare in children. Only a few small series have been published, with little information about long-term progression. The objective of our study was to describe the clinical, radiological and pathological features, and the long-term course of PAP in a cohort of 34 children from La Réunion Island.

miRNA profiles as a predictor of chemoresponsiveness in Wilms' tumor blastema.

The current SIOP treatment protocol for Wilms' tumor involves pre-operative chemotherapy followed by nephrectomy. Not all patients benefit equally from such chemotherapy. The aim of this study was to generate a miRNA profile of chemo resistant blastemal cells in high risk Wilms' tumors which might serve as predictive markers of therapeutic response at the pre-treatment biopsy stage.

Standardization of Gleason grading among 337 European pathologists.

Aims:   The 2005 International Society of Urological Pathology (ISUP) modification of Gleason grading recommended that the highest grade should always be included in the Gleason score (GS) in prostate biopsies. We analysed the impact of this recommendation on reporting of GS 6 versus 7.

Methods And Results:   Fifteen expert uropathologists reached two-thirds consensus on 15 prostate biopsies with GS 6-7 cancer.

Utility of whole slide imaging and virtual microscopy in prostate pathology.

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate.

Interactive digital slides with heat maps: a novel method to improve the reproducibility of Gleason grading.

Our aims were to analyze reporting of Gleason pattern (GP) 3 and 4 prostate cancer with the ISUP 2005 Gleason grading and to collect consensus cases for standardization. We scanned 25 prostate biopsy cores diagnosed as Gleason score (GS) 6-7. Fifteen genitourinary pathologists graded the digital slides and circled GP 4 and 5 in a slide viewer.

Handling and reporting of transurethral resection specimens of the bladder in Europe: a web-based survey by the European Network of Uropathology (ENUP).

Aims: To collect of information about European practices on handling and reporting of transurethral resection specimens of the bladder.

Methods And Results: The European Network of Uropathology is a communication network that includes 335 pathology laboratories in 15 western European countries. A web-based questionnaire was answered by 52.

Transcription factor E3 and transcription factor EB renal cell carcinomas: clinical features, biological behavior and prognostic factors.

Purpose: Translocation renal cell carcinomas represent a distinct clinicopathological entity. Studying the natural history, biological behavior and potential prognostic factors are crucially warranted.

Materials And Methods: We selected 54 patients with renal cell carcinoma with positive nuclear transcription factor E3 and transcription factor EB expression from the Juvenile RCC Network.

Diffuse chondroid malformation of the lung: cases series of a hitherto undescribed congenital lung disease.

Congenital chondroid lesions of the lung are rare pathological findings. They are a constant feature of lung malformations such as giant cystic pulmonary chondroid hamartoma, chondroid cystic malformation, and in the "cartilaginous variant" of congenital adenomatoid malformation. All of these present as a large single thoracic mass.

Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009.

Objective: To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children.

Study Design: Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009.

Results: 21 cases were identified; 62% of the patients were boys.

WNT/beta-catenin pathway activation in Wilms tumors: a unifying mechanism with multiple entries?

Based on characterization of both genomic and expression status of WT1 and CTNNB1 (beta-catenin) in a series of 60 Wilms tumor samples, combined with genome-wide expression profiling of these tumors, normal mature and fetal kidney controls, we show that WT1/beta-catenin expression was a better classifier than WT1/CTNNB1 mutations. We present molecular data supporting that the WNT pathway is involved in both tumor classes, with and without WT1/beta-catenin alterations. In the tumor class with WT1/beta-catenin alterations, we identified overexpression of 14 previously unreported WNT target genes, including TWIST1.

The European Network of Uropathology: a novel mechanism for communication between pathologists.

In pathology there is a need to rapidly disseminate professional information to the appropriate target groups. This is a surprisingly difficult task on an international level. Therefore, the European Network of Uropathology (ENUP) was recently organized by the Uropathology Working Group of the European Society of Pathology.

Interobserver variability between expert urologic pathologists for extraprostatic extension and surgical margin status in radical prostatectomy specimens.

Accurate Gleason score, pathologic stage, and surgical margin (SM) information is critical for the planning of post-radical prostatectomy management in patients with prostate cancer. Although interobserver variability for Gleason score among urologic pathologists has been well documented, such data for pathologic stage and SM assessment are limited. We report the first study to address interobserver variability in a group of expert pathologists concerning extraprostatic soft tissue (EPE) and SM interpretation for radical prostatectomy specimens.

High cyclin E staining index in blastemal, stromal or epithelial cells is correlated with tumor aggressiveness in patients with nephroblastoma.

Purpose: Identifying among nephroblastoma those with a high propensity for distant metastases using cell cycle markers: cyclin E as a regulator of progression through the cell cycle and Ki-67 as a tumor proliferation marker, since both are often deregulated in many human malignancies.

Methodology/principal Findings: A staining index (SI) was obtained by immunohistochemistry using anti-cyclin E and anti-Ki-67 antibodies in paraffin sections of 54 postchemotherapy nephroblastoma including 42 nephroblastoma without metastasis and 12 with metastases. Median cyclin E and Ki-67 SI were 46% and 33% in blastemal cells, 30% and 10% in stromal cells, 37% and 29.

Preoperative Wilms tumor rupture: a retrospective study of 57 patients.

Background: According to current International Society of Pediatric Oncology (SIOP) Wilms recommendations, all preoperative tumor ruptures should be classified as stage IIIc. However, to the authors' knowledge, the definition and diagnostic criteria of preoperative rupture have not been defined clearly.

Methods: The authors performed a retrospective analysis of 57 children with clinical and/or radiologic (computed tomography [CT]) signs of preoperative tumor rupture of a series of 250 patients enrolled in Wilms SIOP protocols at their institution.

Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene expression profiling analysis of 31 cases with a review of the literature.

We report clinicopathologic features of a large series of renal translocation carcinomas from a multicentric study. Diagnosis was performed by cytogenetic examination of fresh material and/or by immunochemistry with antibodies directed against the C-terminal part of transcription factor E3 (TFE3) and native transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic features were assessed.

The 20-core prostate biopsy protocol--a new gold standard?

Purpose: We investigated the ability of a 20-core prostate biopsy protocol to enhance the prostate cancer diagnosis rate.

Materials And Methods: We compared the diagnosis rate of prostate biopsies in 2 groups of consecutive patients, including group 1-10 cores and group 2-20 cores. The prostate specific antigen range in the 2 groups was 3 to 30 ng/ml and biopsies were performed because of increased prostate specific antigen (more than 3 ng/ml) and/or abnormal digital rectal examination.

Expansion of regulatory T cells in patients with Langerhans cell histiocytosis.

Background: Langerhans cell histiocytosis (LCH) is a rare clonal granulomatous disease that affects mainly children. LCH can involve various tissues such as bone, skin, lung, bone marrow, lymph nodes, and the central nervous system, and is frequently responsible for functional sequelae. The pathophysiology of LCH is unclear, but the uncontrolled proliferation of Langerhans cells (LCs) is believed to be the primary event in the formation of granulomas.

Prostate cancer characteristics in a multiracial community.

Objectives: To investigate the hypothesis that Northern Africans differ from Caucasians with regard to their PCa characteristics, using our 1988-2006 database we retrospectively reviewed the preoperative and pathological features of consecutive patients subjected to radical prostatectomy (RP) for localized prostate cancer (PCa) and stratified according to their ethnic origin.

Methods: In 727 consecutive patients (616 Caucasians; 61 Blacks originating from Central Africa and the French West Indies; 50 Northern Africans from Morocco, Algeria, Tunisia), we preoperatively analyzed and compared age, clinical stage of the tumour, prostate-specific antigen (PSA), transrectal ultrasound prostate volume, PSA density (PSAD), biopsy Gleason score, number of positive cores (NPC), and percentage of tissue core invaded by cancer (PTIC); postoperatively, we determined the status of the capsule, seminal vesicles, and margins of the RP specimen, as well as Gleason score and prostate weight. Statistical analyses (chi-square test and ANOVA) were performed to compare the results between the three groups of patients.

Outcome of infants with celiac disease.

Aims: Determine the proportion of infants whose celiac disease (CD) was confirmed in childhood and evaluate their prognosis in adulthood.

Patients And Methods: The diagnosis of CD was established between 1971 and 1982 in 84 infants based on intestinal biopsy data; a gluten-free diet was prescribed and the cohort followed prospectively.

Results: Thirty-six infants were followed less than 5 years.

[Effect of dutasteride on reduction of intraoperative bleeding related to transurethral resection of the prostate].

Objective: The pharmacological action of 5-alpha-reductase inhibitors (5-ARI) would reduce angiogenesis associated with benign prostatic hyperplasia (BPH), thereby decreasing peroperative bleeding during transurethral resection of the prostate (TURP). Dutasteride, a double inhibitor of 5-alpha-reductase iso-enzymes types 1 and 2, was not been previously studied in the context of reduction of peroperative bleeding related to TURP.

Material And Methods: We conducted a multicentre, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy of dutasteride 0.

Sulfated HNK-1 epitope in developing and mature kidney: a new marker for thin ascending loop of Henle and tubular injury in acute tubular necrosis.

The HNK-1 carbohydrate epitope is a 3-sulfo-glucuronyl residue attached to lactosamine structures on glycoproteins, proteoglycans, or glycolipids mostly expressed in the nervous system. Here, using monoclonal antibodies against the sulfated HNK-1 carbohydrate epitope, we first examined its distribution in developing and adult kidneys, then its expression in kidneys with tubular necrosis and renal neoplasms. This HNK-1 epitope was expressed in the human, rabbit, and rat, but not mouse kidney.