Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases.

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

[Use of social media by French urologists: Results from a study of the National French Urological Association]. / Utilisation des réseaux sociaux par les urologues français : résultats d'une étude de l'Association française d'urologie.

PURPOSE: Social Media (SoMe) have changed the face of modern medicine. Our purpose was to make an inventory on the use of SoMe within urologists members of the French Urological Association (AFU). MATERIAL AND METHODS: A 15 questions-survey was sent by email 2 months to urologists AFU members before the 108th French Congress of Urology (#CFU2014). At the same time, the activity of urologists using Twitter was analyzed over the period of the national conference with the symplur software (www.symplur.com). RESULTS: Overall, 270 (17.3%) surveys were completed. Only 50% of responders had an online SoMe account. The most commonly used social media platforms were: Facebook (36.1%) followed by LinkedIn (28.2%), Google+ (19.6%), YouTube (18.7%) and Twitter (17.4%). The use of SoMe was higher in the age groups 30-40 and 40-50 years than in older age groups (83% versus 36%). Only 38.7% of respondents reported using SoMe in a professional field. At the congress #CFU2014, there were over 1000 tweets generated by 173 different contributors. CONCLUSION: Only a minority of French urologists have reported to be connected to SoMe and a predominantly personal use. The emergence of Twitter in French urological conferences is very new but seems promising. Further studies are needed, especially within the members of the residents French urological association to better characterize the true impact of SoMe in urology. LEVEL OF EVIDENCE: 4.

The accuracy of renal tumor biopsy: analysis from a national prospective study.

OBJECTIVE: To assess preoperative renal tumor biopsy (RTB) accuracy. MATERIALS AND METHODS: As part of the prospective NEPHRON study, data from 1,237 renal tumors were collected, including the use and results of RTB and final histology following nephrectomy. During the 6 months period of inclusion, 130 preoperative biopsies were performed. We used the kappa coefficient of the McNemar test to determine the concordance between the biopsy and the nephrectomy specimen (NS) regarding four parameters: malignant/benign status, histological subtype, Fuhrman grade and microscopic necrosis. RESULTS: Preoperative biopsies were performed in 9.7 and 11.4 % of the 667 radical and 570 partial nephrectomies, respectively. Tumor biopsy was inconclusive in 7.7 % of the cases. In 117 cases, a comparison between RTB and NS was available. Benign tumors accounted for three (2.6 %) and five (4.3 %) of the RTB and NS, respectively (κ = 0.769, good). With seven (6 %) discordant results in terms of histological subtype characterization between RTB and final pathology, RTB accuracy was considered excellent (κ = 0.882). In 33 cases (31.7 %), Fuhrman grade was underestimated at biopsy resulting in an intermediate concordance level (κ = 0.498). Tumor microscopic necrosis was identified in 12 RTB (10.4 %) versus 33 NS (28.4 %) (κ = 0.357, poor). CONCLUSIONS: RTB provides good to excellent diagnostic performance for discriminating malignancy and tumor histological subtype. However, its performance is intermediate or even poor when considering prognostic criteria like Fuhrman grade or microscopic necrosis. Thus, this possible inaccuracy should be taken into consideration when using RTB for accurate guidance of treatment strategy.

[Ethics and ritual circumcision]. / Éthique et circoncision rituelle.

Circumcision dates back to ancient times, nowadays, this ritual is practiced mainly in the context of Jewish and Muslim religions. The purpose of this article is to give urologists elements of reflection on the act according to the ethical principles of autonomy, beneficence, non-maleficence and justice. According to a Kantian vision, priority should be given to the respect and wishes of the individuals. In contrast, for the utilitarian theory, circumcision can be justified by a contribution to the happiness of the majority of community members at the expense of a given few. In the event of a request for ritual circumcision, urologists find themselves in the middle, uncomfortable for some, questioning the ethics of its meaning. The main pitfall for the surgeon remains in respecting the child's autonomy.

Nocardia spp infections among hematological patients: results of a retrospective multicenter study.

OBJECTIVES: To describe the clinical characteristics and prognostic factors of hematological patients affected by Nocardia spp infections. METHODS: We retrospectively evaluated all the cases diagnosed in four Italian institutions. RESULTS: Between 2002 and 2012, 10 cases of nocardiosis were recorded. The median age of the patients was 66 years (range 24-85 years). The underlying hematological disease was a lymphoproliferative disorder in all but two patients. Eight patients (80%) showed active underlying hematological disease, relapsed or refractory in five (50%); one patient had a history of previous allogeneic bone marrow transplantation. Eight patients (80%) were on steroid therapy; lymphopenia was present in 8/10 (80%) patients. All patients showed lung involvement. Six patients were affected by disseminated nocardiosis. Three patients (30%) were nocardemic and three (30%) showed central nervous system involvement. Skin, lymph nodes, and bone were involved in one patient each. The median overall survival was 65 days. Older age, a longer period between hematological diagnosis and Nocardia spp infection, and relapsed/refractory hematological disease were associated with a worse prognosis. CONCLUSIONS: Although rare, nocardiosis should be considered in the differential diagnosis of pulmonary and central nervous system lesions among hematological patients. Lymphoproliferative disorders, prolonged steroid treatment, lymphopenia, and active hematological disease are the conditions that are worth considering as predisposing factors for the development of this disease.

Hema e-Chart registry of invasive fungal infections in haematological patients: improved outcome in recent years in mould infections.

The electronic surveillance system Hema e-Chart allowed us to prospectively collect data and to perform an analysis of invasive fungal infections (IFI) diagnosed in febrile patients as well as the procedures allowing their diagnosis and outcome according to the treatment given. Every patient admitted to 26 Italian Haematology Units with a new diagnosis of haematological malignancy and who was a candidate for chemotherapy was consecutively registered between March 2007 and March 2009. In all, 147 haematological patients with mycoses were identified. Yeasts were found in 23 infections; moulds were diagnosed in 17 proven, 35 probable and 72 possible mycoses. Galactomannan (GM) antigen was the most important test to diagnose probable mould infection; it was positive (cut-off >0.5) in 27 (77%) probable and in nine (53%) proven mould infections. Among patients with probable/proven mould infection who received no prophylaxis or non-mould-active prophylaxis with fluconazole, more patients (n = 26, 78.8%) had GM antigen positivity compared with patients (n = 10, 52.6%) given prophylaxis with mould-active drugs (p <0.05). First-line antifungal therapy was effective in 11/23 (48%) yeast infections and in 37/52 (71.2%) proven/probable mould infections. Twenty patients (14%) died within 12 weeks. The fungal attributable mortality was 30.4% and 17.3% in yeast and proven/probable mould infections, respectively. Among risk factors only age was independently associated (p 0.013) with mortality; sex, underlying haematological malignancy, previous prophylaxis and presence of neutropenia at diagnosis were not significant. A diagnosis of mould infection seemed to have a trend for a better outcome than the diagnosis of yeast infection (p 0.064).

[Quality of life after cystectomy: French national survey conducted by the French Association of Urology (AFU), the French Federation of Stoma Patients (FSF) and the French Association of Enterostomy Patients (AFET) in patients with ileal conduit urinary diversion or orthotopic neobladder]. / Qualité de vie après cystectomie: enquête nationale de l'Association française d'urologie (AFU), la Fédération des stomisés de France (FSF) et de l'Association française des entérostomathérapeutes (AFET) chez des patients ayant eu une dérivation urinaire cutanée non continente ou un remplacement vésical orthotopique.

OBJECTIVE: National multicentre study based on specific self-administered quality of life questionnaires in patients with Bricker ileal conduit urinary diversion or orthotopic neobladder. MATERIAL AND METHOD: Questionnaires were distributed by three associations (FSF, AFU, AFET) and comprised general questions and questions specific to the type of diversion. A disability score was also included. RESULTS: Between September 2003 and March 2004, out of a total of 5739 questionnaires, 909 were returned and 877 were analysed: 738 patients with Bricker ileal conduit and 139 with orthotopic neobladder. The two populations differed at the time of the study (Bricker: 69% of men with a mean age of 70 years, orthotopic neobladder: 95.7% of men with a mean age of 64 years). The mean interval since the operation was seven years. Ninety-four percent of patients with Bricker ileal conduit and 93% of patients with orthotopic neobladder were satisfied or very satisfied with the diversion, despite mean disability scores of 5.2+/-3.7 and 3.1+/-3.6, respectively. A correlation between this score and patient satisfaction (Wilcoxon: p<0.0001) was only observed for patients with a Bricker ileal conduit. This score was significantly related to the presence of urinary incontinence with the two types of diversion. Incontinence was frequent (16.1% with Bricker ileal conduit) and 78% of patients feared episodes of incontinence, mainly due to the appliance. Daytime incontinence was frequent for 18.1% of patients with orthotopic neobladder and 40% of patients used at least one protection per day. Out of the patients with neobladder, 82.6% experienced nocturnal incontinence, interfering with sleep in 31.9% of cases. Sexual disorders and altered bowel habit (40%) were very frequent. Stoma-therapy management was insufficient for Bricker ileal conduit and exceptional after bladder replacement. CONCLUSION: Cystectomy with either ileal conduit urinary diversion or orthotopic neobladder alters many aspects of the patient's life, but patients finally accept and adapt to their new way of life.

Efficacy, toxicity and feasibility of a shorter schedule of DCEP regimen for stem cell mobilization in multiple myeloma.

From 2000 to 2004, 152 patients with multiple myeloma aged or=4 x 10(6) cells/kg. The proportion of patients in whom mobilization failed was similar in the two groups. The incidence of WHO grade III neutropenia was higher in group II, although the difference was not statistically significant; the percentage of patients requiring hospitalization for severe infections was similar in the two groups. The incidence of WHO grade IV thrombocytopenia did not differ between the two groups. The response rate was 72% in group I and 80% in group II with similar percentages of patients achieving good responses. DCEP-short is a good mobilizing regimen, sharing the same characteristics as infusional-DCEP: high mobilizing efficacy, low toxicity and good antitumor activity. This new schedule of DCEP does, however, allow complete outpatient management and so could be advantageously included in any high-dose therapy program.

Successful therapy with high-dose steroids and cyclosporine for the treatment of carmustine-mediated lung injury.

The treatment of the pulmonary toxicity induced by carmustine is nowadays based on the use of corticosteroids that generally lead to a rapid resolution of pneumonitis. On the contrary, no therapeutic alternatives are reported for those patients who do not respond to steroids. We describe a case of non-Hodgkin's lymphoma in a patient who developed a severe interstitial pneumonitis after an autologous transplantation including carmustine in the conditioning regimen. He was successfully treated with an association of steroids and cyclosporine A with a rapid improvement of symptoms and a complete resolution of pneumonitis. This is, to our knowledge, the first case of carmustine-induced pneumonitis, resistant to steroids alone, successfully treated with cyclosporine A. This suggests an immunoallergic mechanism in the pathogenesis of the damage, which can be reversed with prompt therapy.

Consolidation treatment with autologous peripheral blood progenitor cell transplantation in acute myeloid leukemia: a single center experience.

Several trials have suggested that intensive post-remission therapy may prolong the duration of complete remission (CR) in acute myeloid leukemia (AML). The purpose of this study was to evaluate the feasibility and the efficacy of high-dose cytarabine (HiDAC) consolidation chemotherapy followed by high-dose therapy and autologous infusion of peripheral blood progenitor cells (PBPC) mobilized by G-CSF in adult patients with AML in first CR. Fifteen consecutive AML patients underwent HiDAC consolidation chemotherapy, used as a method of in vivo purging, followed by G-CSF for the purpose of autologous PBPC collection. Eleven patients collected a median of 6.9x10(8)/kg peripheral blood mononuclear cells (MNC) (range 2.9-23) and a median of 6.67x10(6)/kg CD34+ cells (range 1.8-33.5) with a median of two aphereses (range 1-3). Two patients did not mobilize and two obtained an inadequate number of progenitor cells. The 11 patients with adequate collections received myeloablative chemotherapy followed by the infusion of PBPC. The median number of days to recover neutrophils and platelets was 12 and 13, respectively. After a median follow-up of 28.7 months (range 17.2-43.4), five out of 11 patients who underwent PBPC transplantation are still in CR, five have died in first relapse and one is alive in CR after relapse treated with salvage therapy and second PBPC infusion. These results demonstrate that HiDAC consolidation chemotherapy followed by autologous PBPC transplantation is a feasible procedure with minimal toxicity. Randomized studies should be performed to evaluate whether this form of consolidation may produce a significant improvement in leukemia-free survival.

Trisomy 11 and a complex t(11;11;22) in a patient with acute myelomonocytic leukemia (AML-M4) following myelodysplasia (MDS): a cytogenetic study of a mechanism of leukemogenesis.

We describe a 73-year-old man diagnosed with acute myelomonocytic leukemia (AML-M4) following myelodysplasia with trisomy 11 and with a t(11;11;22). This is the first case with both abnormalities present in the same cells and with the t(11;11;22) involving a chromosome 11 already duplicated at 11q23. This band contains the MLL gene that undergoes partial tandem duplication in patients with +11, which is "promiscuous," being translocated with a large number of genetic partners. Our patient had a complex karyotype that was completely defined by in situ hybridization. This technique demonstrated that the t(11;11;22) derivative with a duplication of band 11q23 carried from three to four copies of MLL. Two copies of the gene were close to each other and centromeric to the break-point region. Therefore, a partial tandem duplication of the MLL gene might have happened before the occurrence of t(11;11;22). Considering the associated chromosome defects, the monosomy for the long arm of chromosome 7, due to an unbalanced translocation t(7;17), further underlines the possibility that a partial tandem duplication of the MLL gene might have taken place.

Acute lymphoblastic leukaemia occurring as second malignancy: report of the GIMEMA archive of adult acute leukaemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

Between July 1992 and June 1996, 901 new cases of adult acute lymphoblastic leukaemia were recorded in the GIMEMA Archive of Adult Acute Leukaemia; 21 of them (2.3%) had a previous primary malignancy (PM). We found that secondary acute lymphoblastic leukaemia cases (sALL) presented with older age, a high incidence of pre-pre-B immunophenotype and a significantly higher prevalence of cancer among relatives compared to de novo ALL. The leukaemogenic activity of the cytotoxic drugs employed for the treatment of PM may have played a potential role in only a proportion of patients, opening the possibility that some sALL patients may have developed two or more malignancies due to individual predisposing factors.

Assessment of renal function in patients with multiple myeloma: the role of urinary proteins.

Renal failure (RF) in multiple myeloma (MM) is considered an ominous complication even though, when timely therapy is started in patients with minimal damage, a high percentage of cases can achieve a regression. The evaluation of renal involvement usually relies on serum creatinine or its clearance, but these parameters have proved to be inadequate to identify initial damage. The aim of this study was to assess the role of the following urinary proteins in diagnosing renal impairment at an early stage: high-molecular-mass proteins (transferrin, IgG, albumin) as markers of glomerular damage, and low-molecular-weight proteins and parenchymal enzymes [alpha(1)-acid glycoprotein (AGP), alpha(1)-microglobulin (alpha(1)M), retinol-binding protein (RBP), beta(2)-microglobulin (beta(2)M), lysozyme (LZ), and N-acetyl-beta-d-glucosaminidase (NAG)] as indicators of tubular disorder. Thirty MM patients (nine at disease onset and 21 previously treated) were included in the study. No correlation was found between the urinary proteins and the phase or the stage of the disease. By the Spearman test, Bence Jones proteinuria correlated significantly with the 24 h proteinuria (p=0. 01) and beta(2)M (p=0.02), and weakly with the alpha(1)M. Serum creatinine concentrations and urea correlated with most of the analytes evaluated: RBP correlated well with urea (p=0.004) and creatinine (p=0.004); IgG (p=0.006) albumin (p=0.009), AGP (p=0.04), and NAG (p=0.02) correlated with serum creatinine. Significant statistical correlation was found between all the analytes except LZ and the creatinine clearance. Twelve of the 30 MM patients (40%) showed abnormal values of urinary proteins. Four of these patients showed overt renal failure with significant modification of the serum parameters and of creatinine clearance, three showed an isolated decrease of creatinine clearance, and five did not present any alteration of serum or urinary parameters. This testifies to the utility of urinary proteins in highlighting renal damage even in cases where the customary serum indicators of renal disorder are normal. In conclusion, our results demonstrate that AGP, RBP, NAG, transferrin, and IgG are good indicators of renal damage. They do not correlate with the severity of the disease, but they seem to be helpful in identifying a subset of patients with initial renal dysfunction.

Management of acute promyelocytic leukemia relapse in the ATRA era.

BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.

A complex translocation (5;7) in a patient with acute nonlymphocytic leukemia evolved from a myelodysplastic syndrome.

Complete or partial monosomy for the long arms of chromosomes 5 or 7 or both is frequently observed in therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia. Sporadic cases have been reported in which partial monosomy is due to unbalanced translocations. The patient described herein carries one such rearrangement. 46,XY,t(1;2) (q32;p23),del(5)(q13),der(7)(5qter-->5q22::7p15-->7 q21:),del(12)(p12), resulting in partial monosomy for the long arms of chromosomes 5 and 7 and in partial monosomy for the short arm of chromosome 7.

Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS.

One hundred and five consecutive primary high-risk myelodysplastic syndromes (MDS) or secondary acute myeloid leukaemia (sAML) evolving from MDS (performance status 0-3, ECOG) entered this study. Induction chemotherapy (CT) consisted of idarubicine 12 mg/m2 i.v. on days 1 and 2, etoposide 60 mg/m2/12h i.v. for 5d, Ara-C 120 mg/ m2/12h i.v. for 5d (one or two courses). Patients were randomized to receive or not G-CSF (5 microg/kg/d subcutaneously 48 h after the end of CT). 52 cases underwent CT alone and 53 CT+G-CSF. The CT+ G-CSF patients had a significantly shorter duration of neutropenia (8 nu 16d) with a lower incidence of infections and significantly better responses (CR+PR: 74% v 52%, P<0.05). 40 patients entered CR: 17 with CT and 2 3 with CT+G-CSF. Responders underwent two consolidation courses with the same CT, followed by high-dose Ara-C (2 g/m2 every 12h for 3 d). Most CRs were clonal. At present 21 responders have relapsed (median relapse-free survival 4 5 months). Eight responders received an allo-BMT, six are alive in CR 7-57 months post-transplant. Therefore allo-BMT only increases the chance of a long survival and possible cure. In conclusion, CT+G-CSF did not prolong either CR duration or survival; the growth factor support, however, increased the number of allo-transplantable cases by inducing higher remission rates and improving clinical conditions.

Efficacy of a combination of idarubicin, etoposide and intermediate-dose cytosine arabinoside as salvage therapy in relapsing or resistant unfavorable lymphoma.

BACKGROUND AND OBJECTIVE: Idarubicin, an anthracycline analogue, is active in non-Hodgkin's lymphoma. This study evaluates the efficacy and toxicity of a combination of idarubicin, etoposide and intermediate-dose cytarabine (IVA) in unfavorable lymphoma in relapse or resistant to prior doxorubicin- or novantrone-based regimens. DESIGN AND METHODS: Thirty patients with relapsing or resistant unfavorable lymphoma received a combination of idarubicin 12 mg/m2 i.v. on day 1, etoposide 60 mg/m2 i.v. every 12 hours for 3 days, and Ara-C 1 g/m2 i.v. every 12 hours for 3 days (3-hour infusion). Median age was 39 years (range: 22-60). All patients had been given prior doxorubicin or novantrone; 54% of them had received 2 or more chemotherapy regimens; 67% of total were in clinical relapse (30% in their second relapse), and 23% had resistant disease. RESULTS: The overall response rate to IVA was 60% (18 of 30 patients). Complete remission rate was 20% (6 of 30) in the whole group, 45% (5 of 11) among patients in their first relapse. Remission median duration was 9 months (range: 1-18), with a 3-year relapse-free and overall survival of 20% and 15%, respectively. Severe neutropenia occurred in 13 patients (43%) and severe thrombocytopenia in 11 patients (37%), with a median duration of 9 and 13 days, respectively. No cardiac toxicity developed; sepsis during neutropenia was documented in four instances and two patients (7%) died of therapy-related events (septic shock). INTERPRETATION AND CONCLUSIONS: Idarubicin combined with etoposide and intermediate-dose cytarabine proved to be an active salvage therapy in unfavorable lymphoma given prior doxorubicin or novantrone; the best results were obtained among patients in their first relapse, with low tumor burden.