RESUMEN
Most patients with KIT D816V(+) advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype and clinical characteristics of 70 multi-mutated KIT D816V(+) advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03), but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, the presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V(+) SM. On the basis of these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM.
Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Mastocitosis Sistémica/genética , Mutación , Proteínas Nucleares/genética , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Represoras/genética , Ribonucleoproteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Mastocitosis Sistémica/sangre , Mastocitosis Sistémica/mortalidad , Persona de Mediana Edad , Riesgo , Factores de Empalme Serina-ArgininaRESUMEN
From 1971-1979, 380 women with marked stress incontinence had urethro-vesical suspensions according to Pereyra. In the majority of the cases this urethrovesical suspension was done as an additional operation to vaginal hysterectomy and anterior and posterior colporrhaphy. The follow-up examination of 189 patients 6 to 60 months after the operation included as for the pre-operative examination the history, the gynaecological findings, the Bonney test, the residual urine determination, chromocystoscopy, urinalysis with culture and sensitivity and a lateral cysto-urethrogram. 86.2% of the patients were objectively and subjectively cured. In 13.8% no improvement of the stress incontinence was found. The Pereyra urethro-vesical suspension is a valuable addition to the operative treatment of urinary stress incontinence. The complication rate is as low as for other methods and the results are at least the same. The Pereyra urethro-vesical suspension is recommended.