Idiotypic characterization of antibody-induced antibody responses

Anti-idiotypic antisera were produced in syngeneic (C57BL/6) mice against a monoclonal anti-Dextran B512 (Dex) antibody (38-13). In radioimmunoassays, anti-idiotypic antibodies were shown to react with the homologous idiotype, while failing to recognize another monoclonal anti-Dex antibody, independently derived from C57BL/6 mice (D-16). Plaque inhibition tests confirmed the specificity of the anti-idiotypic antibodies and revealed that the 38-13 idiotype is expressed by about half of all anti-Dex antibodies produced in C57BL/6, but not in CBA mice. Injection of normal (but not athymic) C57BL/6 mice with low doses of 38-13 monoclonal antibodies, contained culture supernatants or ascitic fluids, resulted in a 10-20 fold increase in the numbers of anti-Dex PFC detected in the spleen 5 days later, the majority of which carried the 38-13 idiotype.     

Post-surgical vestibular schwannoma remnant tumors: What to do?

BackgroundVestibular schwannomas (VS) are benign tumors of the vestibular nerve's myelin sheath. The current trend in VS surgery is to preserve at the facial function, even if it means leaving a small vestibular schwannoma tumor remnant (VSTR) after the surgery. There is no defined therapeutic management VSTR. The aim of this study was to assess the evolution of the VSTR to define the best therapeutic management and identify predictive factors of VSTR progression.MethodsAmong the 256 patients treated surgically for VS in the Department of Neurosurgery at Angers University Hospital, 33 patients with a post-surgical VSTR were included in this retrospective study. For all surgical patients, the data collected were age at diagnosis, the Koos classification, the surgical access, the existence of a type 2 neurofibromatosis (NF2), the TR location and size on control MRI-scans. Patients had a bi-annual follow-up with clinical status and VSTR size assessment with MRI-scan. Survival analyzes were performed to determine the time and rate of VSTR progression, and identify factors of progression.ResultsThe mean follow-up of the population was 51 months. All VS remnant progression occurred between 38 and 58 months after surgery. In non-NF2 patients with first follow-up MRI-scan three months after surgery, 43% presented a spontaneous regression, 50% a stability and 7% a progression of the VSTR. In the same population with the 1-year MR-scan after surgery as baseline, 25% presented a spontaneous regression, 62.5% a stability and 12.5% a VSTR progression. These data are consistent with the data reported in the literature. The post-operative facial function impairment and an initial remnant ≥ 1.5 cm³ were found to be significant risk factors of VS remnant progression in non-NF2 population in univariate analysis (P = 0.048 and 0.031) but not in multivariate analysis.ConclusionIn our experience, the best therapeutic management of the post-surgical VSTP in non-NF2 patients with no risk factor of progression is a simple clinical radiological follow-up otherwise complementary radiosurgery should be considered.     

Cumulative risk of second primary contralateral breast cancer in BRCA1/BRCA2 mutation carriers with a first breast cancer: A systematic review and meta-analysis

BRCA1/2 mutation carriers are at a higher risk of breast cancer and of subsequent contralateral breast cancer (CBC). This study aims to evaluate the evidence of the effect of the BRCA1/2-carriership on CBC cumulative risk in female breast cancer patients.The literature was searched in Pubmed and Embase up to June 2013 for studies on CBC risk after a first primary invasive breast cancer in female BRCA1/2 mutation carriers. A qualitative synthesis was carried out and the methodological quality of the studies evaluated. Cumulative risks of CBC after 5, 10 and 15 years since the first breast cancer diagnosis were pooled by BRCA1/2 mutation status.A total number of 20 articles, out of 1324 retrieved through the search, met the inclusion criteria: 18 retrospective and 2 prospective cohort studies. Cumulative risks of up to five studies were pooled. The cumulative 5-years risk of CBC for BRCA1 and BRCA2 mutation carriers was 15% (95% CI: 9.5%–20%) and 9% (95% CI: 5%–14%), respectively. This risk increases with time since diagnosis of the first breast cancer; the 10-years risk increased up to 27% and 19%, respectively. The 5-years cumulative risk was remarkably lower in non-BRCA carriers (3%; 95% CI: 2%–5%) and remained so over subsequent years (5%; 95% CI: 3%–7%).In conclusion, risk of CBC increases with length of time after the first breast cancer diagnosis in BRCA1/2 mutation carriers. Studies addressing the impact of treatment-related factors and clinical characteristics of the first breast cancer on this risk are warranted.