Malformations, genetic abnormalities, and Wilms tumor.

BACKGROUND: Wilms Tumor (WT) can occur in association with tumor predisposition syndromes and/or with clinical malformations. These associations have not been fully characterized at a clinical and molecular genetic level. This study aims to describe clinical malformations, genetic abnormalities, and tumor predisposition syndromes in patients with WT and to propose guidelines regarding indications for clinical and molecular genetic explorations. PROCEDURE: This retrospective study analyzed clinical abnormalities and predisposition syndromes among 295 patients treated for WT between 1986 and 2009 in a single pediatric oncological center. RESULTS: Clinically identified malformations and predisposition syndromes were observed in 52/295 patients (17.6%). Genetically proven tumor predisposition syndromes (n = 14) frequently observed were syndromes associated with alterations of the chromosome WT1 region such as WAGR (n = 6) and Denys-Drash syndromes (n = 3), syndromes associated with alterations of the WT2 region (Beckwith-Wiedeman syndrome, n = 3), and Fanconi anemia (n = 2). Hemihypertrophy and genito-urinary malformations (n = 12 and n = 16, respectively) were the most frequently identified malformations. Other different syndromes or malformations (n = 10) were less frequent. Median age of WT diagnosis was significantly earlier for children with malformations than those without (27 months vs. 37 months, P = 0.0009). There was no significant difference in terms of 5-year EFS and OS between WT patients without or with malformations. CONCLUSIONS: The frequency of malformations observed in patients with WT underline the need of genetic counseling and molecular genetic explorations for a better follow-up of these patients, with a frequently good outcome. A decisional tree, based on clinical observations of patients with WT, is proposed to guide clinicians for further molecular genetic explorations.

Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network.

BACKGROUND: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients. PATIENTS AND METHODS: Patients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Overall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up. CONCLUSION: In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC.

[New perspectives in prostate cancer management]. / Les nouvelles perspectives de prise en charge du cancer de la prostate.

The treatment of prostate cancer is experiencing important innovations. Hormone therapy includes a new class of drugs: LHRH antagonists, which induce a rapid, fast and sustained reduction of testosterone levels. Active surveillance enables to avoid an aggressive treatment without decreasing survival, provided that strict eligibility and follow-up criteria are applied. New imaging techniques and laboratory assays lead to early diagnosis of small size tumors. Lastly, focal therapy has the potential to target localized cancers without deterioration of surrounding structures. These concomitant improvements offer the clinician and the patient attractive options for prostate cancer management. However, they are not devoid of limitations and constraints. Thus, it is crucial to define the most appropriate patient's profile for each therapeutic option, taking into account the objective characteristics of the tumor and the psychological features of the patient.

[First line indications for hormonal therapy in prostate cancer]. / Cancer de la prostate et hormonothérapie: indications thérapeutiques de première ligne.

The utilization of androgen deprivation therapy in prostate cancer has evolved over time. Unquestionably considered first line treatment in metastatic cancers or in case of lymph node involvement, it is increasingly used in locally advanced and high-risk cancers, combined with radiation therapy. However, the practical modalities of treatment are still controversial (neoadjuvant, concomitant/adjuvant) and should be discussed on a case-by-case basis, taking into account tumor stage and risk level, which depends mainly on Gleason score and PSA levels and kinetics. Hormone therapy is also indicated in case of systemic relapse, especially if PSA doubling time is less than 12 months. LHRH agonists have become the standard care; antiandrogens can be added at the beginning of the LHRH agonist therapy to obtain a complete androgen blockade. Intermittent androgen deprivation therapy has recently proved efficacious and might be more widely used in the future, provided that strict prescription and follow-up recommendations are clearly established.

[Guidelines for the conventional surgical indications for urinary stress incontinence in women (colposuspension, aponeurotic support of the bladder neck]. / Recommandations concernant les indications de la chirurgie conventionnelle de l'incontinence d'urine d'effort de la femme (colposuspension, soutènement aponévrotique du col).

The equivalence of the functional results of the suburethral sling and open colposuspension and the greater morbidity of colposuspension is such that the indications for traditional surgery correspond to the contraindications for suburethral sling: there no longer seem to be but few indications for supporting the bladder neck using an aponeurotic swing; caution recommends preferring colposuspension when the functional result of placing a suburethral sling risks being compromised by either vaginal trophicity abnormalities or previous repair to the urethra such as suburethral diverticulum or urethrovaginal fistula. Laparoscopic colposuspension is not recommended to treat urinary stress incontinence in women. This technique may be warranted if other laparoscopic procedures are necessary and should be carried out by an experienced surgeon trained in this approach.

[Synthesis of the guidelines for the treatment of non-neurological urinary incontinence in women]. / Synthèse des recommandations pour le traitement de l'incontinence urinaire féminine non neurologique.

The last two decades have brought about new medical and surgical treatments revolutionizing care for non-neurological urinary incontinence in women. Many studies, often randomized prospective studies with sufficient follow-up, have validated the therapeutic choices and shown them not to be part of a fad or marketing pressures. The French Association of Urology (L'Association Française d'Urologie), through its Committee on Women's Urology and Pelviperineology (Comité d'Urologie et de Pelvipérinéologie de la Femme), proposes its recommendations. These were established by an expert group of specialists (urologists, gynecologists, and physical therapists), based on a review of the literature but taking into account the daily practices in academic and private practice settings. Between evidence-based medicine and reality in the field, these recommendations attempt to propose realistic and applicable strategies.

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

AIMS: To survey current European practices in handling and reporting of radical prostatectomy (RP) specimens. METHODS AND RESULTS: A European Network of Uropathology (ENUP) was organized for the dissemination of information, survey studies and research collaborations. Contact data of uropathologists were collected from 321 pathology laboratories in 15 West European countries. In the first ENUP survey, 67.6% (217/321) of the members replied to a web-based questionnaire. Some practices were adopted by a large majority, e.g. inking of the specimen (96.6%), Gleason grading (99.5%), stratifying extraprostatic extension (EPE) according to extent (88.2%), reporting TNM stage (88.6%) and reporting location of positive margins (98%). As many as 71.6% of respondents always embedded the entire prostate and only 10.8% always practised partial embedding. Whole mounts were routinely used by 37.5% and standard blocks by 55.5%. Among areas with variable routines were methods to define focal versus extensive EPE and methods to quantify margin positivity, probably reflecting that the optimal method has yet to be determined. CONCLUSIONS: Some practices are almost universally adopted in Europe, whereas others still need to be standardized. The results of the study may be helpful when judging what recommendations are reasonable to issue.

Pseudoneoplastic lesions of the testis and paratesticular structures.

Pseudotumors or tumor-like proliferations (non-neoplastic masses) and benign mimickers (non-neoplastic cellular proliferations) are rare in the testis and paratesticular structures. Clinically, these lesions (cysts, ectopic tissues, and vascular, inflammatory, or hyperplastic lesions) are of great interest for the reason that, because of the topography, they may be relevant as differential diagnoses. The purpose of this paper is to present an overview of the pseudoneoplasic entities arising in the testis and paratesticular structures; emphasis is placed on how the practicing pathologist may distinguish benign mimickers and pseudotumors from true neoplasia. These lesions can be classified as macroscopic or microscopic mimickers of neoplasia.

[Kikuchi-Fujimoto's disease: report of 5 cases and literature review]. / Maladie de Kikuchi-Fujimoto: à propos de 5 cas et revue de la littérature.

Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis is a benign disease predominantly occurring in young women which etiology remains unknown and revealed by cervical lymphadenitis and/or prolonged fever. It has rarely been reported in children. Among the 5 cases reported, 1 child had a systemic localization. The diagnosis is based on the histological examination of a lymph node biopsy. The disease course was spontaneously favourable in 2 cases; a corticotherapy was needed in 3 children. A pathogen agent was found in 2 patients. Kikuchi's disease can reveal or evolve into autoimmune disease particularly lupus, thus a long clinical and biological follow-up is necessary.

[Treatment of childhood cancer in Africa. Action of the Franco-African childhood cancer group]. / Le traitement des cancers de l'enfant en Afrique. Travaux du groupe franco-africain d'oncologie pédiatrique.

The childhood cancer survival rate is currently 75% in industrialized countries. Rates in developing countries are much lower. The Franco-African Childhood Cancer Group (French acronym, GFAOP) was founded in 2000 with aim of reducing this unfavorable situation in Africa. The GFAOP has developed two forms of action. The main form consists of organizing two- to twelve-month training sessions for physicians and nurses in France and Morocco. The other form involves assessing the feasibility of modern treatment protocols for various cancers in Africa. The first feasibility trials were carried out on nephroblastoma and Burkitt's lymphoma in 12 pilot units in North Africa, West Africa, and Madagascar. In the first study from 2001 to 2005 we treated 306 cases of Burkitt's lymphoma using French LMB protocols adapted to the African setting and achieved a survival rate of 61%. A second study started in 2005 using Endoxan alone achieved a highly satisfactory survival rate of 73% for neuroblastoma in all stages except bilateral. Altogether from 2001 to 2007 more than 1000 cases of nephroblastoma and Burkitt's lymphoma were treated in African hospitals by African doctors and nurses. No patients were transferred to Europe. The GFAOP supplied drugs when necessary and took care of most travel expenses. African and French doctors worked together on protocol design, trial management, and data analysis. These promising results show that the latest therapeutic techniques can be used to treat childhood cancer in Africa by adapting the protocol to conditions in developing countries. Sanofi-Aventis Laboratories in association with the International Union against Cancer has launched a major campaign to improve Pediatric Oncology in developing countries. Projects in four GFAOP units are being financed through this campaign. In 2006 the GFAOP began assessment of two new treatment protocols, i.e., one for acute lymphoblastic leukemia and the other for Hodgkin's disease. Two other projects are being planned, i.e., one for treatment of retinoblastoma and the other for treatment of some types of brain tumors.

Correlation of MDR1 gene expression with chemotherapy in neuroblastoma.

Forty-one neuroblastoma tumor specimens have been analyzed by Northern and slot blot hybridization techniques with human MDR1 gene probes. Only one of 15 (6%) tumors from patients who had not received chemotherapy exhibited high levels of MDR1 transcripts, while 11 of 26 (42%) treated tumors showed high levels of MDR1 expression (Fisher exact test: P = .03). The results indicate that the level of MDR1 mRNA expression is associated with previous chemotherapy, including drugs that select the multidrug resistance phenotype in vitro regardless of neuroblastoma tissue origin or N-myc content in the genome. For the 26 treated neuroblastomas, the number of nonresponsive tumors was found to be significantly higher among those with high levels of MDR1 mRNA.

[Understanding nephroblastoma. Information dedicated to parents and relatives]. / Comprendre le néphroblastome. Information à l'usage des parents et des proches d'un enfant malade.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information developed in this program is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres,the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding nephroblastoma is an adapted version of various scientific publications and international clinical practice guidelines, validated by oncology experts and by the Nephroblastoma Committee of the French Society against Cancers and Leukaemias in children and adolescents (SFCE). It was elaborated with the active participation of parents and other family members. It is meant to provide a basis for the explanation of the disease, to help parents asking questions, and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 PARIS, Tel. (0033)1 76 64 78 00, www.fnclcc.fr). This document was validated at the end of 2005 and published in May 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding nephroblastoma and published in this edition of the Cancer et Radiothérapie, describe the physiopathology of nephroblastoma, as well as treatments and follow-up. The guide allows parents and relatives to better understand the disease and the treatments proposed. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

Combined analysis of DNA ploidy index and N-myc genomic content in neuroblastoma.

The aim of the study was to assess, in a group of nonselected patients with neuroblastoma, the prognostic value of both N-myc gene amplification and DNA ploidy index, taking into account potential confounding factors such as age and stage. Of 59 patients studied, 23 were younger than 1 year at diagnosis, 31 presented with stage IV, 10 with stage III, 5 with stage II, 8 with stage I, and 4 with stage IV-S. N-myc genomic content was analyzed by Southern blot hybridization technique and N-myc amplification (greater than or equal to 3 copies/haploid genome) was present in 6 stage IV, 2 stage III, and 1 stage IV-S. The DNA ploidy index was analyzed by flow cytometry. Of the 59 neuroblastomas, 26 were diploid (DNA index, 1) and 33 were aneuploid (DNA index, greater than 1). The majority of the aneuploid tumors (28 of 33) were near-triploid with DNA indexes between 1.25 and 1.68, 4 were near-diploid (DNA index up to 1.18), and 1 was hypotetraploid (DNA index, 1.85). The proportion of near-triploid tumors was significantly greater among patients under 1 year of age and among patients presenting with stages I, II, and IV-S. Interestingly, 0 of 28 near-triploid neuroblastomas exhibited N-myc gene amplification, compared to 9 of 31 in the group of diploid, near-diploid, and hypotetraploid tumors (Fisher's exact test, P less than 0.001). Four factors were significantly related to a high risk of relapse in univariate analysis, i.e., age, stage, DNA index, and N-myc amplification. In multivariate analysis, only N-myc amplification and the DNA index remained significantly associated with a high risk of relapse. The 2-year disease-free survival rate was 94% (95% confidence interval, 77-98%) for patients with near-triploid neuroblastoma, compared to 45 and 11% (95% confidence interval, 32-70 and 4-23%) for patients with diploid or near-diploid tumors, without and with N-myc amplification, respectively. We concluded that the combination of N-myc and DNA index should be included in routine management of neuroblastoma.

[Prenatal ultrasound diagnosis of neuroblastoma]. / Neuroblastomes de diagnostic échographique anténatal.

With the progress of foetal ultrasonography, diagnosis of foetal tumors can be made before birth. We report five cases of prenatally detected neuroblastoma of the adrenal glands. Diagnosis was made during the third trimester in all cases. At birth no clinical sign related to the tumor was present, and urinary catecholamines were within normal ranges. On ultrasound scans the tumor was cystic in 1 case, solid in 2 cases and of mixed echogenicity in 2 cases. All children were operated on without pre or postoperative chemotherapy. In each setting the tumor was a stage I neuroblastoma according to the Evans classification. All children are alive and disease-free with a follow-up of 32 months at 14 years.

[Disseminated fusarium infection in two neutropenic children]. / Fusariose disséminée chez deux enfants neutropéniques.

UNLABELLED: Disseminated fusariosis in children is a rare and serious fungal infection, that occurs especially in neutropenic immunosuppressed patients, treated for malignant hemopathy, or bone marrow transplant recipient. Treatment is difficult and mortality is estimated between 50 and 70% in adult patients. CASE REPORT 1: A ten-year-old boy, treated for an acute lymphoblastic leukemia in second relapse, presented a disseminated fusarium spp infection, that occurred during neutropenia. He died due to fusariosis infection in spite of amphotericin B treatment. CASE REPORT 2: A ten-year-old neutropenic girl, treated for an acute myeloïd leukemia, presented disseminated fusariosis, uncontrolled by amphotericin B. Recovery was observed after voriconazole introduction and resolution of neutropenia. Ten months later, she presented a leukemia's relapse, treated by new intensive chemotherapy with secondary prophylaxis by voriconazole, without fusariosis's recurrence. CONCLUSION: Voriconazole, a new triazole agent, seems to be an alternative antifungal agent to amphotericin B for disseminated fusarium infection, either at the acute phase or for secondary prophylaxis.

Establishment and characterization of a human adrenocortical carcinoma xenograft model.

Adrenocortical carcinomas are rare malignant tumors. They have a poor prognosis, as they are often diagnosed late and are usually resistant to chemotherapy. The lack of a suitable animal model for these tumors has been a major obstacle to the evaluation of new therapeutic agents. The aim of this study was to establish and characterize xenografts of the human adrenocortical carcinoma NCI H295R cell line as a model of adrenocortical carcinoma for future therapeutic trials. This cell line was sc injected (6 x 10(6) cells) into nude mice (n = 20). Solid tumors were locally measurable after 45 days at 90% of the inoculation sites. The xenografts were similar histologically to the original adrenocortical carcinoma from which the cell line was derived. The xenografts precisely reproduced the dysregulation of the insulin-like growth factor (IGF) system [overexpression of the IGF-II and IGF-binding protein-2 (IGFBP-2) genes] typical of adrenocortical carcinoma. Similarly to adrenocortical carcinomas, human IGFBP-2 (but not IGF-II) was secreted in mouse plasma. We analyzed steroid production (cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, delta4-androstenedione, 11-deoxycortisol, corticosterone, and testosterone). Xenografts produced all three class of steroids, with the preferential production of androgens of the delta4 pathway. The H295R xenograft model is a good model of human adrenocortical carcinoma, as it mimics dysregulation of the IGF system usually found in these tumors. It also produces IGFBP-2 and steroids that can be used as tumor markers. This model may therefore be useful for evaluating therapeutic agents.

Osteochondromyxoma of bone: a congenital tumor associated with lentigines and other unusual disorders.

This article describes the clinical and pathologic features of four unusual bone tumors. Three were congenital or most likely so; the fourth, detected at age 1 year, was probably of considerable duration. The patients, three boys and one girl, each presented with a painless mass. Two had the Carney complex, a familial lentiginous and multiorgan tumorous syndrome; another probably had this disorder; the fourth did not show it, but his mother did. The tumors occurred in the nasal region (n = 2) and the diaphysis of the tibia and radius (n = 1 each). Roentgenographically, three had benign characteristics; the fourth, malignant features. Grossly, the tumors were gelatinous, cartilaginous. and bony. Microscopically, they featured benign-appearing polymorphic cells with few division figures arranged in sheets and lobules set in a myxomatous, cartilaginous, osseous, and hyaline fibrous matrix. Cellularity was low to moderate. The tumors eroded bone, one infiltrated between bony trabeculae, and three had soft tissue extension. Complete resection of one tumor was curative; incomplete excision of two tumors resulted in local recurrence (intracranial and fatal) in one and persistence in the other; the fourth tumor remains under observation after biopsy. No tumor metastasized.

Occupational risks of bladder cancer in France: a multicentre case-control study.

The relationships between occupational risk factors in France and bladder cancer were assessed from a hospital-based case-control study conducted between 1984 and 1987 in five regions representing various industries, including mining, textile manufacture, metallurgy and the production of rubber and chemicals. The study concerned 765 cases (658 men and 107 women) and the same number of controls. Odds ratios (OR) adjusted for matching variables (age, place of residence and hospital), and tobacco smoking were estimated by unconditional logistic regression. A significantly increased risk of bladder cancer was observed among men employed in coal mining (OR = 2.42; 95% confidence interval (Cl) : 1.25-4.67) and the chemicals industry (OR = 2.36; 95% Cl : 1.23-4.53). Aircraft and ship's officers (OR = 11.8; 95% Cl : 1.46-95.7), managers (OR = 1.64; 95% Cl : 1.11-2.43) and street vendors (OR = 3.60; 95% Cl : 1.15-11.3) also had an increased risk. Among women, employment in the clothing industry was associated with a high OR (= 3.21; 95% Cl : 1.34-7.71). Assessment of individual exposures by a panel of industrial hygiene experts showed that significantly more cases than controls had been exposed to the following substances: chlorinated solvents (OR = 1.86; 95% Cl : 1.19-2.90), industrial oils and greases (OR = 1.44; 95% Cl : 1.10-1.89), welding fumes (OR = 1.40; 95% Cl : 0.98-2.01), coal dust (OR = 1.71; 95% Cl : 1.02-2.89) and metallic oxide dust (OR = 2.99; 95% Cl : 1.12-8.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Two new cases of papillary renal cell carcinoma with t(X;1)(p11;q21) in females.

Two cases of papillary renal cell carcinoma (RCC) with a karyotype 46,X,t(X;1)(p11.2;q21) in two female patients aged 9 and 29 years are reported. These observations, and the review of the 17 reported cases with a translocation at band Xp11 confirm that this abnormality delineates a clinicopathological entity within the classical papillary RCC, characterized by the early age of occurrence and, probably, distinct histological features. Including these two new female cases, the sex ratio in cases with t(X;1) appears similar to that observed in the other papillary RCC.