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.

[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.

[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.

[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.

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.

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.

[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.

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.

[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.

[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.

Prostate saturation biopsy in the reevaluation of microfocal prostate cancer.

PURPOSE: We evaluated the ability of an extended, 32-core repeat transrectal ultrasound prostate biopsy protocol to improve the characterization of low volume, well differentiated disease in men with a diagnosis of potentially insignificant microfocal prostate cancer, as defined by 1 single focus positive core of 10 with less than 5 mm of Gleason score 6 or less tumor on primary biopsy. MATERIALS AND METHODS: A total of 35 consecutive patients, who were 62 to 75 years old, had a median serum prostate specific antigen of 8 ng/ml (range 0.5 to 14) and a diagnosis of minimal prostate cancer, and were willing to consider observation with delayed treatment at progression, were offered repeat saturation prostate biopsy with a median of 32 cores (range 18 to 36) under local anesthesia. This biopsy was to determine whether more extensive prostate sampling would confirm or disprove the initial diagnosis of microfocal, well differentiated prostate cancer. RESULTS: The procedure was aborted in 1 patient because of massive rectal hemorrhage. Another patient had acute prostatitis with gram-negative sepsis. Of 34 evaluable biopsy sets 11 (32%) were negative for cancer, suggesting that tumor detected at the primary biopsy was probably of low volume and amenable to observation with delayed treatment. Of the biopsies 23 (68%) were positive, 17 were at multiple sites and 7 were upgraded to Gleason score 7 or greater. These patients were then considered to have significant tumors and were offered active treatment. CONCLUSIONS: This study is to our knowledge the first to describe the clinical use of prostate saturation biopsies for re-evaluating potentially insignificant prostate cancer. Of patients with minimal disease on standard 10-core biopsy, results show that this technique may be helpful for distinguishing the 30% who probably have minimal disease based on negative repeat saturation biopsy from the 70% who almost certainly have a significant tumor, as characterized by multiple positive cores, with or without an increased Gleason score. The latter patients should be offered active therapy.

Risks and benefits of hormonal manipulation as monotherapy or adjuvant treatment in localised prostate cancer.

A round table meeting was held to discuss the role of hormonal therapy in localised prostate cancer. The findings of the group were that immediate hormonal therapy does not provide an overall survival advantage in localised and locally advanced prostate cancer. Bicalutamide can prolong disease free survival in patients with locally advanced prostate cancer, however it is important to underline that at this time it has not been shown to influence disease specific nor overall survival. It remains also unproven that early treatment is superior to treatment at progression. However, a trend towards decreased survival with bicalutamide was observed in low risk patients such as those with localised disease. In patients receiving bicalutamide, there were increased cardiovascular side-effects, in addition to the high incidence of gynaecomastia. Early hormonal therapy has to be balanced against such side-effects and the inevitable appearance of hormone refractory disease in patients who progress after hormonal therapy. Consequently, patients with localised, low risk disease are not considered appropriate candidates for hormonal therapy used either as mono-therapy or in the adjuvant setting.

Micro-focal prostate cancer: a comparison of biopsy and radical prostatectomy specimen features.

OBJECTIVES: To study the pathologic features of radical prostatectomy (RP) specimens of patients operated on the basis of a potentially "Insignificant" prostate cancer (Ca P) characterized by one single focus (less than 3mm) of moderately differentiated adenocarcinoma - Gleason score < or =6, out of 6-10 biopsies and to determine which characteristics, if any, are predictive of the presence of a "non significant" prostate cancer in the specimen characterized by a low volume (<0.5 ml) moderately differentiated organ confined, cancer (Gleason score less than 6). PATIENTS AND METHODS: PSA, biopsy features, and surgical specimens of a series of 56 patients submitted to RP for "insignificant Ca P" on TRUS prostate biopsies between 1988 and 2004 were compared regarding the number of tumor foci, Gleason grade and score, tumor volume determined by the cylinder method, as well as extraprostatic extension (EPE) and positive surgical margins (P.SM.). RESULTS: 70% of the patients had multifocal microfocal cancer apart from the index tumor. The presence of grade 4 was ignored by the biopsy in 50% of the cases, however the primary grade was correctly evaluated in more than 70% of the biopsy sets. 42% of the patients had a cancer volume less than 0.5 ml and 29% met the definition of insignificant/unimportant cancer characterized by a moderately differentiated (Gleason score < or =6) of low volume (less than 0.5 ml) however no feature accurately predictive of insignificant cancer could be individualized. In this whole series, only 8% of the patients had EPE. When the pre-operative PSA was <10 ng/ml, 98% of the patients had an organ confined tumor. CONCLUSION: Patients diagnosed with prostate cancer on the basis of one single focus less than 3 mm of moderately differentiated (Gleason < or =6) prostate cancer have 30% of chances of harboring an insignificant tumor in their prostate and are therefore, at risk of being overtreated, however there is at this time no specific feature able to identify these patients pre operatively.

[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.