Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

Using Discrete Event Simulation to Model the Economic Value of Shorter Procedure Times on EP Lab Efficiency in the VALUE PVI Study.

BACKGROUND: The VALUE PVI study demonstrated that atrial fibrillation (AF) ablation procedures and electrophysiology laboratory (EP lab) occupancy times were reduced for the cryoballoon compared with focal radiofrequency (RF) ablation. However, the economic impact associated with the cryoballoon procedure for hospitals has not been determined. OBJECTIVE: Assess the economic value associated with shorter AF ablation procedure times based on VALUE PVI data. METHODS AND RESULTS: A model was formulated from data from the VALUE PVI study. This model used a discrete event simulation to translate procedural efficiencies into metrics utilized by hospital administrators. A 1000-day period was simulated to determine the accrued impact of procedure time on an institution's EP lab when considering staff and hospital resources. The simulation demonstrated that procedures performed with the cryoballoon catheter resulted in several efficiencies, including: (1) a reduction of 36.2% in days with overtime (422 days RF vs 60 days cryoballoon); (2) 92.7% less cumulative overtime hours (370 hours RF vs 27 hours cryoballoon); and (3) an increase of 46.7% in days with time for an additional EP lab usage (186 days RF vs 653 days cryoballoon). Importantly, the added EP lab utilization could not support the time required for an additional AF ablation procedure. CONCLUSIONS: The discrete event simulation of the VALUE PVI data demonstrates the potential positive economic value of AF ablation procedures using the cryoballoon. These benefits include more days where overtime is avoided, fewer cumulative overtime hours, and more days with time left for additional usage of EP lab resources.

Vdrive Evaluation of Remote Steering and Testing in Lasso Electrophysiology Procedures Study: The VERSATILE Study in Atrial Fibrillation Ablation.

INTRODUCTION: Circular mapping catheters (CMC) are an essential tool in most atrial fibrillation ablation procedures. The Vdrive™ with V-Loop™ system enables a physician to remotely manipulate a CMC during electrophysiology studies. Our aim was to compare the clinical performance of the system to conventional CMC navigation according to efficiency and safety endpoints. METHODS AND RESULTS: A total of 120 patients scheduled to undergo a CMC study followed by pulmonary vein isolation (PVI) were included. Treatment allocation was randomized 2:1, remote navigation:manual navigation. The primary effectiveness endpoint was assessed based on both successful navigation to the targeted pulmonary vein (PV) and successful recording of PV electrograms. All PVs were treated independently within and between patients. The primary safety endpoint was assessed based on the occurrence of major adverse events (MAEs) through seven days after the study procedure. Primary effectiveness endpoints were achieved in 295/302 PVs in the Vdrive arm (97.7%) and 167/167 PVs in the manual arm (100%). Effectiveness analysis indicates Vdrive non-inferiority (pnon-inferiority = 0.0405; δ = -0.05) per the Cochran-Mantel-Haenszel test adjusted for PV correlation. Five MAEs related to the ablation procedure occurred (three in the Vdrive arm-3.9%; two in the manual arm-2.33%). No device-related MAEs were observed; safety analysis indicates Vdrive non-inferiority (pnon-inferiority = 0.0441; δ = 0.07) per the normal Z test. CONCLUSION: Remote navigation of a CMC is equivalent to manual in PVI in terms of safety and effectiveness. This allows for single-operator procedures in conjunction with a magnetically guided ablation catheter.

Comparison of resource utilization of pulmonary vein isolation: cryoablation versus RF ablation with three-dimensional mapping in the Value PVI Study.

BACKGROUND: Point-to-point focal radiofrequency (RF) catheter ablation for aberrant pulmonary vein triggers that manifest into atrial fibrillation (AF) is the traditional method for treating symptomatic drug-resistant paroxysmal AF (PAF) when an ablation procedure is warranted. More recently, pulmonary vein isolation (PVI) using the cryoballoon has been demonstrated to be safe and effective (STOP AF clinical trial). Currently, two small studies have reviewed the procedural efficiency when comparing cryoballoon to focal RF catheter ablation procedures; however, no multicenter study has yet reported on this comparison of the two types of ablation catheters. METHODS: A multicenter retrospective chart extraction and evaluation was conducted at seven geographically mixed cardiac care centers. The study examined procedural variables during ablation for PVI in PAF patients. RESULTS: In several procedural measurements, the two modalities were comparable in efficiencies, including: acute PVI >96%; length of hospital stay at approximately 27 hours; and about 30% usage of adenosine after procedural testing. However, when compared to RF catheters, the cryoballoon procedure demonstrated a 13% reduction in laboratory occupancy time (247 min vs 283 min), a 13% reduction in procedure time (174 min vs 200 min), and a 21% reduction in fluoroscopy time (33 min vs 42 min). Additionally, when comparing the material usage of both cryoballoon and RF catheters, the cryoballoon used more radiopaque contrast agent (78 cc vs 29 cc) while using less intraprocedural saline (1234 cc vs 2386 cc), intracardiac echocardiography (88% vs 99%), three-dimensional electroanatomic mapping (30% vs 87%), and fewer transseptal punctures (1.5 vs 1.9). CONCLUSION: This study is the first United States multicenter examination to report the procedural comparisons between the cryoballoon and focal RF catheters when used for the treatment of PAF patients. In this hospital chart review study, potential advantages were found when operating the cryoballoon with regard to hospital resource allocation. There was no statistical difference between cryoballoon and RF catheters for acute PVI success during the ablation procedure.

[Chemotherapy in male external genital organs (testicular and penile cancer)]. / Chimiothérapie des organes génitaux externes chez l'homme (cancer du testicule et du pénis).

AIM: To describe drugs used in the chemotherapy of testis and penis neoplasms. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: Nowadays, the chemotherapy is perfectly codified in adjuvant treatment or in first-line treatment of metastatic testis cancer. A single dose of carboplatin for seminoma testicular (stage I) in adjuvant treatment situation is one of the latest advances. Concerning penis cancer, the optimal protocols validated by a high level of evidence are missing. CONCLUSION: The chemotherapy in testis and penis neoplasms knew few advances in recent years. So, it is necessary to include patients in clinical research protocols.

Effect of HIV genotypic drug resistance testing on the management and clinical course of HIV-infected children and adolescents.

The clinical utility of genotypic drug resistance testing (DRT) in HIV-infected children on antiretroviral therapy (ART) is not well understood. HIV-infected patients aged <19 years undergoing DRT for virological failure were retrospectively enrolled. Indications for DRT and changes in HIV RNA load were recorded. Between January 2000 and December 2006, 57 patients had DRT. The most common indication for DRT was poor ART adherence (57.7% of patients). ART was changed in 50.9% of patients after DRT. Poor adherence was cited by clinicians for not changing ART significantly more often than any other reason (47.3%, P < 0.001). After DRT, significant improvement in HIV RNA load occurred independent of ART changes, though patients whose ART was modified were more likely to become undetectable (31.5% versus 7.0%, P < 0.001). Poor adherence was a significant factor for ordering DRT and for not changing ART in HIV-infected children.

Neuropsychological function and cerebral metabolites in HIV-infected youth.

The effects of HIV on brain metabolites and cognitive function are not well understood. Sixteen HIV+youths (15 vertical, 1 transfusion transmissions) receiving combination antiretroviral therapy and 14 age-matched HIV- youths (13-25 years of age) were evaluated with brain two-dimensional (2D) magnetic resonance spectroscopy (MRS) at 3 Tesla (T) and a neuropsychological battery that assessed three cognitive domains (attention/processing speed, psychomotor ability, and executive function). The relationship between brain metabolite ratios and cognitive performance was explored. Compared to HIV- controls, HIV+ subjects had higher sycllo-inositol (Scy)/total creatine (tCr) (+32%, p = 0.016) and higher Scy/total choline (tCho) (+31%, p = 0.018) on 2D-MRS in the right frontal lobe. HIV+ subjects also had higher glutamate (Glu)/tCr (+13%, p = 0.022) and higher Glu/tCho (+15%, p = 0.048) than controls. HIV+ subjects demonstrated poorer attention/processing speed (p = 0.011, d = 1.03) but similar psychomotor and executive function compared to HIV- controls. The attention/processing score also correlated negatively with the ratio of N-acetylaspartate (NAA) to tCr on 2D-MRS (r = -0.75, p = 0.0019) in the HIV- controls, but not in the HIV+ subjects (Fisher's r-z transformation, p < 0.05). Our results suggest that attention/processing speed is impacted by early HIV infection and is associated with right hemisphere NAA/tCr. Scy and Glu ratios are also potential markers of brain health in chronic, lifelong HIV infection in perinatally infected youths receiving antiretroviral therapy.

Evolution of class A G-protein-coupled receptors: implications for molecular modeling.

Class A or rhodopsin-like G-protein-coupled receptors (GPCRs) constitute the largest transmembrane receptor family of the human genome. Because of their biological and pharmaceutical importance, the evolutionary history of these receptors has been widely studied. Most studies agree on the classification of the 700 members of this family into a dozen of sub-families. However, the relationship between these sub-families remains controversial and the molecular processes that drove the evolution and diversification of such a large family have still to be determined. We review here the evolutionary analyses carried out on class A GPCRs either by phylogenetic methods or by multidimensional scaling (MDS). We detail the key molecular events driving the evolution of this receptor family. We analyze these events in view of the recently resolved crystal structures of GPCRs and we discuss the usefulness of evolutionary information to help molecular modeling.

Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?

BACKGROUND: Sunitinib is a standard of care for metastatic renal cell carcinoma (mRCC). Hypothyroidism is frequently observed under sunitinib therapy. This study was conducted to prospectively determine the correlation between thyroid function and progression-free survival (PFS) in this population. PATIENTS AND METHODS: One hundred and eleven mRCC patients treated with sunitinib were evaluated for serum thyroid-stimulating hormone (TSH) and T4 levels before treatment and every 6 weeks during treatment. Survival was analysed according to a landmark method with a cut-off of 6 months, excluding early progressive or early-censored patients. RESULTS: Out of the 102 patients with normal baseline thyroid function, 53% developed thyroid dysfunction, including 95% hypothyroidisms out of which 90.9% received L-thyroxine replacement. Median time to TSH alteration was 5.4 months. Median PFS was 11.7 months for the entire population. Median PFS was not different between the groups with abnormal or normal thyroid function after 6 months of treatment (18.9 and 15.9 months, respectively, log-rank P = 0.94, hazard ratio = 1.02, 95% confidence interval = 0.54-1.93). There was no difference even after adjustment for Memorial Sloan-Kettering Cancer Centre classification and therapy line. CONCLUSIONS: Abnormal thyroid function with hormonal substitution did not increase survival in our population, independent of initial prognosis and previous treatments. Larger comparative studies are deserved to validate these conclusions.

[Chemotherapy in urologic oncology]. / Chimiothérapie en oncologie urologique.

Chemotherapy is an effective treatment in urologic cancers either for localized tumor or metastatic disease. In urologic cancers, chemotherapy always takes part in a multidisciplinary strategy including surgery, oncology and radiotherapy. Except for metastatic testicular germ cell cancers, chemotherapy is a palliative treatment in other metastatic urologic cancers such as bladder and castration-resistant prostate carcinomas. In metastatic clear cell renal carcinomas, it has not any indication and anti-angiogenic drugs are the only therapeutic options. Neoadjuvant chemotherapy in non-metastatic muscle-invasive bladder cancers must be considered as a standard treatment in fit patients.

A study of 28 flat bone osteosarcomas: prognostic factors and early and long-term outcome.

Limited information is available on clinical management of Flat Bone Osteosarcomas (FBOS). We retrospectively analysed prognostic factors and outcome. Twenty-eight patients were treated in our institution. Survival curves were obtained by the Kaplan-Meier method and compared with the log-rank test. The overall survival (OS) rates at 5 and 10 years were 52.4% and 45.8% respectively. The event-free survival (EFS) rates at 5 and 10 years were 41.5%. The factors influencing EFS in univariate analysis were location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and adequate local tumour control. Location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and local recurrence were statistically correlated with OS. Multivariate analysis retained metastatic disease at diagnosis as prognostic factors of EFS and OS. Our results suggest a more favourable outcome of FBOS as the use of a treatment scheme based on the protocols for long bone osteosarcomas. However, an adequate local treatment is essential to ensure a better outcome.

Roseomonas mucosa isolated from bloodstream of pediatric patient.

We report a case of catheter-related bacteremia associated with Roseomonas mucosa isolated from an immunocompromised pediatric patient with a history of multiple episodes of urinary tract infection and bacteremia.

[Antiangionic drugs in soft tissue sarcoma]. / Antiangiogènes dans les sarcomes des tissus mous.

Angiogenesis is an essential prerequisite in the growth and dissemination of soft tissue sarcoma. The understanding of the VEGF and VEGFR pathway implication in the development of non GIST soft tissue sarcoma and the discovery of the antitumoral activity of drugs that inhibit this pathway in other solid tumors, led to the development of antiangiogenic drugs anti VEGF in soft tissue sarcoma, as monoclonal antibody (bevacuzimab) or as small molecules (tyrosine-kinase inhibitors anti VEGFR). This manuscript presents the results of the first clinical trials that have evaluated the efficacy and safety of some angiogenesis inhibitors in soft tissue sarcomas.

Resection of residual masses after chemotherapy for advanced non-seminomatous germ cell tumours, a monocentric analysis of pre-operative prognosticators.

Removal of residual masses after chemotherapy in non-seminomatous germ cell tumours (NSGCTs) remains the standard of care. We evaluated in a retrospective and monocentric study potential prognostic factors. Fifty-one patients underwent surgery after chemotherapy for NSGCT. We estimated event-free survival with Kaplan-Meier method and used Cox proportional hazards regression analysis to assess the prognostic significance of risk factors. Histology of residual masses revealed fibrosis in 25 (49%), mature teratoma in 18 (35%) and viable germ cells in 8 (16%). Alpha-fetoprotein mean level at diagnosis was higher in patients with residual masses showing mature teratoma and/or viable malignant cells (P = 0.036). In multivariate analysis, poor prognosis group according to International Germ Cell Cancer Collaborative Group was associated with worse outcome compared with good and intermediate prognosis groups (hazard ratio for events = 26.4; 95% confidence interval 2.46-283.9; P = 0.006) and primary testicular NSGCT was associated with better event-free survival than extragonadal NSGCTs (hazard ratio for events = 0.04; 95% confidence interval 0.004-0.48; P = 0.01). Resection of residual masses after chemotherapy in NSGCT results in favourable long-term survival in most patients. Our results compared favourably with those reported from higher volume centres.

Safety, vaccine virus shedding and immunogenicity of trivalent, cold-adapted, live attenuated influenza vaccine administered to human immunodeficiency virus-infected and noninfected children.

OBJECTIVE: To assess the safety of live, attenuated influenza vaccine (LAIV) administered to relatively asymptomatic or mildly symptomatic HIV-infected children and non-HIV-infected children. METHODS: Twenty-five non-HIV and 24 HIV-infected children (CDC Class N or A1,2) were enrolled into this double blind, placebo-controlled study. Children were randomized within each HIV status group to one of two dosing regimens: Regimen 1, Dose 1 = LAIV, Dose 2 = placebo, Dose 3 = LAIV; or Regimen 2, Dose 1 = placebo, Dose 2 = LAIV, Dose 3 = LAIV. Study doses were separated by 28 to 35 days. Reactogenicity events within 10 days and adverse events within 28 to 35 days after each study dose were recorded. Blood HIV RNA concentrations, CD4 counts and CD4% were measured throughout the study on HIV-infected children. Quantitative influenza cultures were performed on nasal aspirates collected periodically from all children up to 28 to 35 days after each study dose. Influenza isolates were assessed for retention of the temperature-sensitive phenotype. Serum influenza HAI antibodies were measured before and after each LAIV vaccination. RESULTS: No significant differences were found in rates of reactogenicity events and vaccine-related adverse events after placebo or the first dose of LAIV within each HIV status group, nor were differences found between HIV-infected and HIV-uninfected children after each dose of LAIV. Overall none of the HIV-infected children experienced a significant LAIV-related serious adverse event or influenza-like illness, making the one sided 95% CI of such a serious event occurring after LAIV 0 to 12%. No significant changes in geometric mean HIV RNA concentrations, CD4 counts or CD4% or prolonged or increased quantity of LAIV virus shedding occurred in HIV-infected children after receiving either dose of LAIV. All recovered influenza isolates retained the temperature-sensitive phenotype. After two doses of LAIV, 83% of the non-HIV-infected and 77% of the HIV-infected children had a > or = 4-fold rise in influenza antibody to at least one of the three LAIV strains. CONCLUSION: If relatively healthy HIV-infected children become exposed to LAIV inadvertently, then serious adverse outcomes would not be expected to occur frequently.

[Tick-born encephalitis]. / L'encéphalite virale à tiques.

INTRODUCTION: Tick-borne encephalitis (TBE), a disease contracted through tick bites, is caused by a Flavivirus. Its geographical distribution comes from the geographical distribution of the reservoir of infection--i.e., mainly the tiny mammals living in the forests and bushes. The endemic area spreads from the Rhine to the Urals, from Scandinavia to Italy and Greece. CURRENT KNOWLEDGE AND KEY POINTS: Symptoms usually evolve in three phases: at first a nonspecific phase with fever and myalgia, then an afebrile phase, and finally a phase with neurological manifestations, such as meningitis, meningoencephalitis and/or myelitis, and fever. Motor neurological sequelae are possible. The cases occurring in the East are characterized by their greater severity compared to those occurring in the West. The diagnosis, easily established given a history of a tick bite in an endemic area, is confirmed by the presence of specific IgM in the blood and/or cerebral spinal fluid. FUTURE PROSPECT AND PROJECTS: There is no specific treatment. Prevention consists of individual prophylactic measures (self-examination and systematic extraction of ticks after exposure, use of repellents), and in immunization. The vaccine, prepared from inactivated viruses, should be used for target populations, that is, for people exposed to tick bites during their professional or leisure outdoor activities.

Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team.

The use of recombinant CD4-IgG2 in pediatric human immunodeficiency virus type 1 (HIV-1) infection was evaluated by single and multidose intravenous infusions in 18 children in a phase 1/2 study. The study drug was well tolerated, and dose proportionality was observed in terms of area under time-concentration curve and peak serum concentration. Acute decreases of >0.7 log(10) copies/mL in serum HIV-1 RNA concentration were seen in 4 of the 6 children treated with 4 weekly 10 mg/kg doses. At 14 days after treatment, 3 children had sustained reductions in serum HIV-1 RNA; the other children had rebounded to baseline levels or above. By 28 days after therapy, the peak HIV-1 cellular infectious units was reduced in all 6 children, including the 2 who had experienced an earlier transient increase in values. Thus, recombinant CD4-IgG2 treatment of HIV-1-infected children appears to be well tolerated and capable of reducing HIV-1 burden.

Recovery of replication-competent virus from CD4 T cell reservoirs and change in coreceptor use in human immunodeficiency virus type 1-infected children responding to highly active antiretroviral therapy.

Highly active antiretroviral therapy (HAART) suppresses plasma viremia in most patients with human immunodeficiency virus (HIV) infection. Prospective study of HIV-infected children (n=27) shows that, in 8 of 12 who responded to HAART (>/=0.5 log reduction in plasma HIV RNA), HAART restricted the number of coreceptors used by the predominant HIV isolate (mean number of coreceptors used at baseline was 4, vs. 1 coreceptor used at 6 months after treatment). This decrease was most striking in 6 of 8 children whose HIV coreceptor tropism changed from X4-tropic at baseline to R5-tropic. In 6 of 10 children tested, with plasma HIV RNA levels of <50 copies/mL, R5-tropic virus was isolated from CD4 T cell reservoirs. All the responding children had a significant increase in naive CD4 T cells (P<.05). These results show that persistent HIV T cell reservoirs are present in children and that HAART may influence the number and type of coreceptors used by the predominant virus isolate.