Tratamiento de tumores de células Leydig del testículo: ¿puede la cirugía conservadora de testículo reemplazar la orquiectomía radical? Resultados de una revisión sistemática / Treatment of leydig cell tumours of the testis: can testis-sparing surgery replace radical orchidectomy? Results of a systematic review

Introducción: El modelo de referencia para los tumores de células de Leydig todavía se considera la orquiectomía radical, pero la cirugía conservadora de testículo en conjunción con la congelación intraoperatoria de secciones ha sido recientemente tratada con resultados prometedores. Adquisición de evidencia: Se identificaron estudios mediante búsquedas en bases de datos electrónicas y exploración de las listas de referencias de los artículos. Se llevó a cabo una búsqueda bibliográfica que abarca el período comprendido entre enero de 1980 a diciembre 2012 mediante las bases de datos PubMed/MEDLINE y EMBASE. Se consideraron las búsquedas adicionales a mano de las listas de referencias de los estudios incluidos, opiniones, metaanálisis y guías sobre el manejo quirúrgico de TCL de los testículos. Síntesis de evidencia: El presente análisis se basa en un total de 13 estudios que cumplían con los criterios de inclusión predefinidos. Un total de 247 participantes se incluyeron en los 13 estudios examinados en esta revisión sistemática. Ciento cuarenta y cinco fueron tratados con orquiectomía radical y 102 con TSS. En el grupo de cirugía radical 7 estudios informaron del seguimiento de los pacientes que va desde 6 a 249 meses. En el grupo de TSS 10 estudios informaron del seguimiento de los pacientes que va desde 6 a 192 meses. La congelación de secciones se realizó en un total de 96 pacientes. La sensibilidad fue del 87,5%. Ninguno de los pacientes tratados con TSS presentó una recurrencia metastásica, mientras que en los pacientes tratados con orquiectomía radical 3 pacientes presentaron recurrencia metastásica. Nuestro análisis añade información completa a las recientes directrices internacionales, que es altamente recomendable realizar un procedimiento de preservación de órganos en cada lesión intraparenquimatosa pequeña. Conclusiones: Los resultados confirman el curso favorable de TCL tratados con TSS. Los resultados obtenidos son alentadores y el concepto es atractivo para convertirse en el tratamiento estándar en todos los pacientes, y no solo en las personas afectadas por la (sub) fertilidad o con testículo solitario

Introduction: The gold standard for Leydig cell tumours (LCTs) is still considered radical orchidectomy, but testis sparing surgery (TSS) in conjunction with intraoperative frozen section (FSE) has been recently attempted with promising results. Acquisition of evidence: Studies were identified by searching electronic databases. A bibliographic search covering the period from January 1980 to December 2012 was conducted using PubMed/MEDLINE and EMBASE database. Studies were excluded if they were single case reports, meeting abstracts and conference proceedings. Synthesis of evidence: The present analysis is based on a total of 13 studies that fulfilled the predefined inclusion criteria. A total of 247 participants were included in the 13 studies examined in this systematic review. 145 were treated with radical orchiectomy and 102 with TSS. In the radical surgery group, the follow-up varied from 6 to 249 months). In the TSS group, the follow-up varied from 6 to 192 months. Frozen section was performed in a total of 96 patients. Sensitivity was 87.5%. None of the patients treated with TSS presented a metastatic recurrence, while in patients treated with radical orchiectomy three patients presented with metastatic recurrence. In selected cases radical surgery appears excessive and the potential for a shift to TSS as the standard management is gathering momentum. Conclusions: The results confirm the favourable course of LCT treated with TSS. The results obtained are encouraging and the concept is attractive to become the standard therapy in all patients and not only in people affected by (sub)fertility or with solitary testis

Treatment of leydig cell tumours of the testis: Can testis-sparing surgery replace radical orchidectomy? Results of a systematic review. / Tratamiento de tumores de células Leydig del testículo: ¿puede la cirugía conservadora de testículo reemplazar la orquiectomía radical? Resultados de una revisión sistemática.

INTRODUCTION: The gold standard for Leydig cell tumours (LCTs) is still considered radical orchidectomy, but testis sparing surgery (TSS) in conjunction with intraoperative frozen section (FSE) has been recently attempted with promising results. ACQUISITION OF EVIDENCE: Studies were identified by searching electronic databases. A bibliographic search covering the period from January 1980 to December 2012 was conducted using PubMed/MEDLINE and EMBASE database. Studies were excluded if they were single case reports, meeting abstracts and conference proceedings. SYNTHESIS OF EVIDENCE: The present analysis is based on a total of 13 studies that fulfilled the predefined inclusion criteria. A total of 247 participants were included in the 13 studies examined in this systematic review. 145 were treated with radical orchiectomy and 102 with TSS. In the radical surgery group, the follow-up varied from 6 to 249 months). In the TSS group, the follow-up varied from 6 to 192 months. Frozen section was performed in a total of 96 patients. Sensitivity was 87.5%. None of the patients treated with TSS presented a metastatic recurrence, while in patients treated with radical orchiectomy three patients presented with metastatic recurrence In selected cases radical surgery appears excessive and the potential for a shift to TSS as the standard management is gathering momentum. CONCLUSIONS: The results confirm the favourable course of LCT treated with TSS. The results obtained are encouraging and the concept is attractive to become the standard therapy in all patients and not only in people affected by (sub)fertility or with solitary testis.

In vivo dynamics of the 103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in HIV-infected patients: preliminary results.

Due to the preferential selection of the fittest HIV mutants, drug-resistant variants are often overgrown by wild-type virus after treatment interruption. Our objective was to investigate the dynamics of the 103N mutation (which usually does not reduce HIV fitness) following the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Patients who were found to have the 103N mutation at or after failure of a NNRTI were selected from an observational database. Two groups of patients were identified: one which continued antiretroviral treatment without NNRTIs (group A) and one which discontinued all anti-retrovirals after failure of an NNRTI (group B). Genotype was obtained by direct sequencing of the replicating plasma virus. Sixty-two subjects tested between July 1998 and December 2002 were included in the analysis, 39 in group A and 23 in group B. At the time of the first resistance test, median (IQR) CD4+ T-lymphocytes and HIV-RNA were 269 (150-449) cells/microL and 25,000 (9,600-83,300) copies/mL. In 31 (50%), 30 (48%), and one case (2%), the 103N mutation was selected by nevirapine, efavirenz, and by delavirdine, respectively. A total of 149 tests were analyzed, with a median (IQR) of 2 (2-3) tests/patient. The median (IQR) interval between failure of NNRTIs and the last resistance test was 11 (5-22) months. Overall, a reversion to wild-type at position 103 was observed in 23/62 (37%) subjects, 14/39 (36%) in group A and 9/23 (39%) in group B. In group A, 14/23 (61%) patients tested within 12 months, 10/16 (63%) of those tested between 12 and 24 months, and 12/14 (86%) of those tested beyond 24 months from NNRTI discontinuation had the 103N mutation. In group B, 14/20 (70%) patients tested within 12 months, 3/4 (75%) of those tested between 12 and 24 months, and none out of two tested beyond 24 months from NNRTI discontinuation had the 103N mutation. In conclusion, following NNRTI discontinuation, in the majority of patients HIV variants carrying the 103N mutation are not overgrown for long by wild-type quasispecies at this position. This suggests that the 103N mutation per se influences minimally the viral fitness in vivo.

Gadobenate dimeglumine 0.5 M solution for injection (MultiHance) pharmaceutical formulation and physicochemical properties of a new magnetic resonance imaging contrast medium.

OBJECTIVE: To characterize the proton-magnetic relaxation properties and complexation equilibria of gadobenate dimeglumine and to develop a pharmaceutical formulation for injection. METHODS: Proton-magnetic relaxivities were determined at 20 MHz and 39 degrees C. Metal complexation was studied potentiometrically. Degradation pathways were identified through prolonged exposure to elevated temperature. RESULTS: Because of its size and very weak interaction with serum albumin, gadobenate dimeglumine has proton-magnetic relaxivities that are larger than those of gadopentetate dimeglumine in both water and biological fluids. With regard to metal complexation, the two products are indistinguishable. The metal complexation behavior and thermal stability of the product allowed a pharmaceutical formulation for injection containing 0.5 M gadobenate dimeglumine without excipients. The physicochemical properties of the formulated product were determined. CONCLUSION: Gadobenate dimeglumine has an elevated T1-relaxivity, especially in blood plasma. The high stability of the complex guarantees a negligible release of gadolinium ion. Gadobenate dimeglumine 0.5 M solution for injection has a shelf life of three years.

Stereoselective pharmacokinetics of moguisteine metabolites in healthy subjects.

We studied the pharmacokinetics of moguisteine, a racemic non-narcotic peripheral antitussive drug, in 12 healthy male subjects after a single oral administration of 200 mg. The unchanged drug was absent in plasma and urine of all subjects. Moguisteine was immediately and completely hydrolyzed to its main active metabolite, the free carboxylic acid M1. Therefore, we evaluated the kinetic profiles of M1, of its enantiomers R(+)-M1 and S(-)-M1, and of M1 sulfoxide optical isomers M2/I and M2/II by conventional and stereospecific HPLC. Maximum plasma concentrations for M1 (2.83 mg/l), M2/I (0.26 mg/l) and M2/II (0.40 mg/l), were respectively reached at 1.3, 1.6 and 1.5 h after moguisteine administration. Plasma concentrations declined after the peak with mean apparent terminal half-lives of 0.65 h (M1), 0.88 h (M2/I) and 0.84 h (M2/II). Most of the administered dose was recovered in urine within 6 h from moguisteine treatment. The systemic and renal clearance values indicated high renal extraction ratio for all moguisteine metabolites, and particularly for M1 sulfoxide optical isomers. Plasma concentration-time profiles and urinary excretion patterns for M1 enantiomers R(+)-M1 and S(-)-M1 were quite similar. Thus, for later moguisteine pharmacokinetic evaluations the investigation of the plasma concentration-time curve and the urinary excretion of the sole racemic M1 through non-stereospecific analytical methods may suffice in most cases.