RESUMEN
Toxoplasma gondii is the causative agent of toxoplasmosis, an infectious disease that affects over 30% of the human world population, causing fatal infections in immunocompromised individuals and neonates. The life cycle of T. gondii is complex, and involves intermediate hosts (birds and mammals) and definitive hosts (felines, including domestic cats). The innate immune repertoire against the parasite involves the production of neutrophil extracellular traps (NET), and neutrophils from several intermediate hosts produce NET induced by T. gondii. However, the mechanisms underlying NET release in response to the parasite have been poorly explored. Therefore, the aims of this study were to investigate whether neutrophils from cats produce NET triggered by T. gondii and to understand the mechanisms thereby involved. Neutrophils from cats were stimulated with T. gondii tachyzoites and NET-derived DNA in the supernatant was quantified during the time. The presence of histone H1 and myeloperoxidase was detected by immunofluorescence. We observed that cat neutrophils produce both classical and rapid/early NET stimulated by T. gondii. Inhibition of elastase, intracellular calcium, and phosphatidylinositol 3-kinase (PI3K)-δ partially blocked classical NET release in response to the parasite. Electron microscopy revealed strands and networks of DNA in close contact or completely entrapping parasites. Live imaging showed that tachyzoites are killed by NET. We conclude that the production of NET is a conserved strategy to control infection by T. gondii amongst intermediate and definitive hosts.
RESUMEN
The study evaluates the clinical and pathological findings of 16 patients with locally advanced penile carcinoma (PC) submitted to emasculation, and discusses questions related to the usefulness of bilateral orchiectomy. Between 1999 and 2010, 172 patients with PC were treated. Sixteen (9%) underwent emasculation. Data were retrieved from the institution's database including age, ethnicity, date of surgery, residential setting, level of schooling, time to diagnosis, type of reconstruction, complications, tumor stage and grade, vascular and perineural invasion along with invasion of corpus cavernosum, corpus spongiosum, testicles, scrotum and urethra. A total of 16 patients (average: 63.1 years) with locally advanced PC were included. All were illiterate or semiliterate rural dwellers and 87% were white. The time to diagnosis was 8-12 months. The mean follow-up time was 31.9 months (1-119). By the time of the last follow-up, only seven patients (43.75%) were alive. Tumors were pT4 (n = 6), pT3 (n = 8), pT2 (n = 2), Grade I (n = 5) and Grade II (n = 11). The histopathological examination revealed invasion of the urethra (n = 13), scrotum (n = 5) and testicles (n = 1). The surgical margin was positive in one patient. Six patients (37.5%) had vascular invasion and 11 (68.7%) had perineural invasion. Currently, only one of the former is alive. The finding of focal microscopic testicular infiltration in only one of 32 testicles, even in the presence of clinically apparent scrotal invasion, suggests that emasculation without bilateral orchiectomy is a safe treatment option for patients with locally advanced PC.
Asunto(s)
Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas/cirugía , Orquiectomía/métodos , Neoplasias del Pene/cirugía , Testículo/cirugía , Carcinoma de Células Escamosas/patología , Estudios de Seguimiento , Estimación de Kaplan-Meier , Tratamientos Conservadores del Órgano/métodos , Pronóstico , Neoplasias del Pene/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: The study evaluates the clinical and pathological findings of 16 patients with locally advanced penile carcinoma (PC) submitted to emasculation, and discusses questions related to the usefulness of bilateral orchiectomy. MATERIALS AND METHODS: Between 1999 and 2010, 172 patients with PC were treated. Sixteen (9 %) underwent emasculation. Data were retrieved from the institution's database including age, ethnicity, date of surgery, residential setting, level of schooling, time to diagnosis, type of reconstruction, complications, tumor stage and grade, vascular and perineural invasion along with invasion of corpus cavernosum, corpus spongiosum, testicles, scrotum and urethra. RESULTS: A total of 16 patients (average: 63.1 years) with locally advanced PC were included. All were illiterate or semiliterate rural dwellers and 87% were white. The time to diagnosis was 8-12 months. The mean follow-up time was 31.9 months (1-119). By the time of the last follow-up, only seven patients (43.75%) were alive. Tumors were pT4 (n = 6), pT3 (n = 8), pT2 (n = 2), Grade I (n = 5) and Grade II (n = 11). The histopathological examination revealed invasion of the urethra (n = 13), scrotum (n = 5) and testicles (n = 1). The surgical margin was positive in one patient. Six patients (37.5%) had vascular invasion and 11 (68.7%) had perineural invasion. Currently, only one of the former is alive. CONCLUSIONS: The finding of focal microscopic testicular infiltration in only one of 32 testicles, even in the presence of clinically apparent scrotal invasion, suggests that emasculation without bilateral orchiectomy is a safe treatment option for patients with locally advanced PC.
