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.

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.

[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.

[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.

[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.

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.

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.

Growth factors in the therapy of myelodysplasia: biological aspects.

Growth factors (GF) are reported to play an important role in the therapy of myelodisplastic syndromes (MDS). After in vitro administration a consistent group of MDS may respond to GF but the possibility of differentiation, regulation or expansion of myelodisplastic clones following GF therapy is still a question to be answered as their optimum dose and combinations. To validate if in vivo treatment with GF, may promote the regulation or the recovery of myelopoiesis and/or modify the clonality of the responses, we gave G-CSF after intensive chemotherapy in high risk MDS and acute leukemia evolving from MDS patients. According to our data the use of G-CSF after intensive chemotherapy may improve the CR rate without increase of leukemic transformation. However the answer were clonal and the remission duration remained very short so we suggest to utilize this time to perform other therapeutic strategies such as, when possible, the BMT.

[Tendinopathy and fluoroquinolones]. / Tendinopathies et fluoroquinolones.

Tendinopathies, essentially involving the Achilles tendon, which tendon rupture, can be secondary to treatment with fluoroquinolones, and facilitated by corticosteroid therapy, renal failure and sport. Fluoroquinolone treatment must therefore be prescribed cautiously and patients must be advised to stop treatment at the slightest warning signs of tendinitis.

[Quality of life and skin urinary diversions. Results of a questionnaire completed by 73 patients]. / Qualité de vie et dérivations urinaires cutanées. Résultats d'un questionnaire adressé à 73 patients.

UNLABELLED: The objective of this study was to evaluate the quality of life of patients with a cutaneous urinary diversion. MATERIAL AND METHODS: A 25-item self-administered questionnaire was sent to 73 patients with a cutaneous urinary diversion, either non-continent (NCD), such as a transileal cutaneous ureterostomy, or continent (CD), such as a Mainz or Kock reservoir. RESULTS: 66 patients answered the questionnaire: 34 NCD and 32 CD. The mean follow-up was 69.2 years for NCD and 58 years for CD. No significant difference was demonstrated between the two samples in terms of the interference of their diversion with their everyday life. Most patients declared that their sex life was now "severely disturbed". However, 3 patients regained a sexual activity after their diversion. Patients with an ideal conduit presented a higher incidence of stoma problems. Overall, 90% of patients with an NCD and 97% of those with a CD were satisfied or very satisfied with their diversion. CONCLUSION: Regardless of the type of diversion, patients were satisfied with their operation. When a cutaneous diversion is necessary, the choice of a continent or non-continent diversion cannot be solely based on the argument of "continence". The best possible choice, as a function of surgical limitations and the patient's desires, can only be determined on the basis of a dialogue between the surgeon and the patient.

[Contribution of computed tomography in the staging of upper urinary tract urothelial tumors. Importance of the tumor diameter measurement]. / Apport de la tomodensitométrie dans la stadification des tumeurs urothéliales de la voie excrétrice supérieure. Importance de la mesure du diamètre tumoral.

OBJECTIVES: To demonstrate a correlation between abdominal computed tomography (CT) data and the histological stage of upper urinary tract tumour (UUTT) in order to more accurately define therapeutic indications. MATERIALS AND METHODS: From 1984 to 1995, 51 patients were treated for UUTT and were assessed by preoperative abdominal CT. 41 of the 51 CT scans were considered to be interpretable and were reviewed retrospectively by a single radiologist. The CT stage and tumour diameter were compared to the pathological stage. RESULTS: CT staging had a reliability of 76%, by combining stages Ta-T2, which could not be distinguished. The sensitivity of CT to assess invasion of the renal parenchyma and ureteric or perirenal fat was 100% and 70%, respectively, with a specificity of 82% and 97%. The accuracy can be improved by decreasing the thickness of sections of the tumour. Tumour diameters (d) of pyelocaliceal tumours, measured by CT and pathology, were closely correlated (r2 = 0.83). All UUTTs less than 3 cm in diameter were found to be superficial on histology. CT correctly estimated the size of these small tumours in 14/15 cases. Overall, by setting the limit at 3 cm, CT was able to detect a superficial pyelocaliceal tumour with a specificity of 92% and a PPV of 93%; however, a CT size > or = 3 cm is not predictive of the histological stage of the lesion. CONCLUSIONS: CT is still imprecise for the staging of UUTT, as it cannot distinguish between Ta, T1 and T2 lesions, and is still not sufficiently reliable in the assessment of invasion of the periurothelial fat or of the renal parenchyma. CT measurement of the diameter of pyelocaliceal tumours can provide an argument in favour of the superficial nature of the lesion and therefore guide the therapeutic decision towards a conservative approach.

[Does magnetic resonance imaging allow the assessment of the loco-regional extension of cancer of the prostate? Report of 27 anatomo-radiologic comparisons]. / L'imagerie par Résonance Magnétique permet-elle d'apprécier l'extension loco-régionale du cancer de la prostate? A propos de 27 confrontations anatomo-radiologiques.

27 patients with histologically proven prostatic carcinoma were investigated by magnetic resonance imaging (MRI) (0.5 Tesla) in order to determine the local spread of the cancer. These patients then underwent ilio-obturator lymph node dissection with frozen section examination, followed by radical prostatectomy. Histological examination of the resection specimens was performed on slides prepared from large transverse sections every 5 mn. The MRI examination was especially designed to confirm the diagnosis of capsular effraction based on the signals of the periprostatic fat (PF), periprostatic venous plexuses (PVP) and seminal vesicles (SV). An abnormality of at least one of these structures was considered to indicate the diagnosis of capsular effraction. The MRI data were compared to the histological findings. The results demonstrated a sensitivity of 62% for the PF signal, 52% for the PVP signal and 40% for the SV signal. The overall MRI-Histology correlation was found to be exact in 23 out of 27 cases (Accuracy = 85%). All of our four errors represented understaging (Sensitivity = 81%). When a rigorous methodology is respected, the high accuracy and sensitivity of MRI makes this modality an investigation of choice for the study of the prostatic capsule, as part of the routine staging of prostatic cancer. It should allow a better selection of patients with intracapsular cancer (T1-2), who constitute candidates for radical treatment.

[Can the prostatic capsule be preserved during cystectomy for bladder tumors: a study of urethral and prostatic involvement in the cystectomy specimens]. / Peut-on préserver la coque prostatique au cours des cystectomies pour tumeur de vessie: étude de l'atteinte urétrale et prostatique sur les pièces de cystectomie.

OBJECTIVES: To evaluate the frequency of urethral and prostatic lesions on cystectomy specimens for bladder tumour. MATERIAL AND METHODS: This retrospective histological study was based on 260 specimens: radical cystectomies performed in 7 operative sites. The prostate and urethra were analysed in 3 planes (upper, middle and lower thirds). The apex was studied separately. Urethral invasion was identified by continuity of the tumour or by the presence of vesical CIS. RESULTS: Urethral involvement is frequent (30.6% cases) essentially due to contiguous invasion (43/80). CIS is the second pathological association (44 urethral CIS/75 bladder CIS). Prostatic adenocarcinoma was present in 17.8% of cases with a Gleason score > 6 for 30% of lesions. CONCLUSION: The high frequency of urethral and prostatic involvement does not justify preservation of the prostate during cystectomy. A serial prospective study should define the precise criteria able to minimize the risk of conservative surgery.

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).

Hypospadias: the release of chordee without dividing the urethral plate and onlay island flap (92 cases)

Standard teaching states that the correction of fibrous chordee requires division of the urethral plate. Subsequently, it is necessary to reconstruct the urethra using tubular urethroplasty, which carries a significant incidence of complications, for example stenosis. In fact, we have demonstrated that it is possible to release severe chordee associated with hypospadias simply by dissecting the urethral plate of the corpora rather than dividing it. Between 1989 and 1993 we operated on 101 patients with hypospadias with fibrous chordee. The release of chordee was achieved without dividing the plate in 92 patients (91%), including all 71 cases of penile hypospadias, 11 perineal hypospadias and 10 reoperations. A total of 92 urethroplasties was performed with an onlay flap and 19 complications occurred in 15 patients.

Thrombotic events are not exclusive to the remission induction period in patients with acute lymphoblastic leukemia: a report of two cases of cerebral sinus thrombosis.

It is well established that in acute lymphoblastic leukemia (ALL) patients L-asparaginase (L-Ase) provokes thrombotic events reducing coagulation inhibitors in both adults and children. A tight correlation between thrombotic and hemorrhagic complications and ALL has also been hypothesized because of the high incidence of disseminated intravascular coagulation (DIC) found during the early period of chemotherapeutic treatment apart from L-Ase. All the authors reporting on this subject, however, consider the remission induction phase of treatment the most risky, if not exclusive, for the development of a thrombotic event, in particular if it includes the administration of L-Ase. We report here two cases of ALL patients who experienced a cerebral sinus thrombosis in a later phase of treatment, demonstrating that the thrombotic risk is surely exacerbated by chemotherapy but is not exclusive to the remission induction period.