Advances in the treatment of prolactinomas

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future

Biochar suppresses N₂O emissions while maintaining N availability in a sandy loam soil

Nitrous oxide (N2O) from agricultural soil is a significant source of greenhouse gas emissions. Biochar amendment can contribute to climate change mitigation by suppressing emissions of N2O from soil, although the mechanisms underlying this effect are poorly understood. We investigated the effect of biochar on soil N2O emissions and N cycling processes by quantifying soil N immobilisation, denitrification, nitrification and mineralisation rates using 15N pool dilution techniques and the FLUAZ numerical calculation model. We then examined whether biochar amendment affected N2O emissions and the availability and transformations of N in soils. Our results show that biochar suppressed cumulative soil N2O production by 91% in near-saturated, fertilised soils. Cumulative denitrification was reduced by 37%, which accounted for 85–95 % of soil N2O emissions. We also found that physical/chemical and biological ammonium (NH4+) immobilisation increased with biochar amendment but that nitrate (NO3−) immobilisation decreased. We concluded that this immobilisation was insignificant compared to total soil inorganic N content. In contrast, soil N mineralisation significantly increased by 269% and nitrification by 34% in biochar-amended soil. These findings demonstrate that biochar amendment did not limit inorganic N availability to nitrifiers and denitrifiers, therefore limitations in soil NH4+ and NO3− supply cannot explain the suppression of N2O emissions. These results support the concept that biochar application to soil could significantly mitigate agricultural N2O emissions through altering N transformations, and underpin efforts to develop climate-friendly agricultural management techniques

Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis

BACKGROUND: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. METHODS: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), resection rate, R0-resection rate, and grade 3-4 adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. RESULTS: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n=20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% CI: 60.1 - 74.6), the R0-resection rate was 83.9% (95% CI: 76.8 - 89.1). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data was obtained for 20 studies representing 283 BRPC patients. Patient-level median OS was 22.2 months (95% CI: 18.8 - 25.6), patient-level median PFS was 18.0 months (95% CI: 14.5 - 21.5). Pooled event rates for grade 3-4 adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI: 10.3 - 28.3), diarrhea (11.1 per 100 patients, 95% CI: 8.6 - 14.3), and fatigue (10.8 per 100 patients, 95% CI 8.1 - 14.2). No deaths were attributed to FOLFIRINOX. CONCLUSION: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial

Erratum: Global disorders of sex development update since 2006: perceptions, approach and care (Hormone Research in Paediatrics (2016) 85 (158-180) DOI: 10.1159/000442975)

In the appendix of the recent publication by Lee et al. entitled 'Global disorders of sex development update since 2006: perceptions, approach and care' [Horm Res Paediatr 2016;85:158–180, DOI: 10.1159/000442975], Massimo Di Grazia, Psychologist, is incorrectly mentioned to be from Cosenga, Italy. The correct city is Trieste, Italy