Surgical management of giant pituitary neuroendocrine tumors: Meta-analysis and consensus statement on behalf of the EANS skull base section.

The optimal surgical treatment for giant pituitary neuroendocrine tumors(GPitNETs) is debated. The aim of this paper is to optimize the surgical management of these patients and to provide a consensus statement on behalf of the EANS Skull Base Section. We constituted a task force belonging to the EANS skull base committee to define some principles for the management of GPitNETs. A systematic review was performed according to PRISMA guidelines to perform a meta-analysis on surgical series of GPitNETs. Weighted summary rates were obtained for the pooled extent of resection and according to the surgical technique. These data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. 20articles were included in our meta-analysis, for a total of 1263 patients. The endoscopic endonasal technique was used in 40.3% of cases, the microscopic endonasal approach in 34% of cases, transcranial approaches in 18.7% and combined approaches in 7% of cases. No difference in terms of gross total resection (GTR) rate was observed among the different techniques. Pooled GTR rate was 36.6%, while a near total resection (NTR) was possible in 45.2% of cases. Cavernous sinus invasion was associated with a lower GTR rate (OR: 0.061). After surgery, 35% of patients had endocrinological improvement and 75.6% had visual improvement. Recurrent tumors were reported in 10% of cases. After formal discussion in the working group, we recommend the treatment of G-PitNETs tumors with a more complex and multilobular structure in tertiary care centers. The endoscopic endonasal approach is the first option of treatment and extended approaches should be planned according to extension, morphology and consistency of the lesion. Transcranial approaches play a role in selected cases, with a multicompartmental morphology, subarachnoid invasion and extension lateral to the internal carotid artery and in the management of residual tumor apoplexy

Variation in flexural, morphological, and biochemical leaf properties of eelgrass (Zostera marina) along the European Atlantic climate regions

Seagrasses need to withstand hydrodynamic forces; therefore, mechanical properties such as flexibility or breaking resistance are beneficial for survival. The co-variation of leaf breaking properties with biochemical traits in seagrasses has been documented, but it is unknown if the same patterns apply to leaf flexural properties. To interpret changes in the ecological function of seagrass ecosystems based on acclimation responses to environmental changes, it is necessary to understand the factors that affect flexural leaf properties. Here, morphological and flexural leaf properties of the perennial type of Zostera marina across different environmental conditions along European Atlantic climate regions are presented together with C:N ratio and neutral detergent fibre content as descriptors of biochemical leaf composition. Eelgrass leaves from cold regions were similar to threefold more elastic and similar to tenfold more flexible, were also narrower (1.7-fold), and contained similar to 1.9-fold higher fibre content than from plants growing in warmer regions. Eelgrass also showed acclimation to local conditions such as seasonality, water depth, and hydrodynamic exposure. Leaves collected from exposed or shallower locations or during winter were more flexible, suggesting an avoidance strategy to hydrodynamic forcing, which is generally higher under those conditions. Flexural rigidity was almost equally controlled by bending modulus (35%) and leaf thickness (37%), indicating functional differences compared to leaf breaking described in the literature. Overall, the findings indicate that Zostera marina has a high flexural plasticity and high acclimation capacity to some climate change effects such as sea level rise and increase in storm frequency and intensity.German Science FoundationGerman Research Foundation (DFG) [PA 2547/1-1]Royal Swedish Academy of Sciences (KVA travel grant)FCT-Foundation for Science and TechnologyPortuguese Foundation for Science and Technology [UID/Multi/04326/2019, SFRH/BPD/119344/2016

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

Progression of colorectal cancer may follow either of two main genetic routes: the chromosome- or microsatellite-instability pathways. Association between the patients' prognosis and microsatellite instability has been questioned. Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells. In this study, the expression of HLA-DR antigen was investigated by immunohistochemistry in 357 large bowel carcinomas stratified by microsatellite instability status. Sixteen per cent of the tumours showed strong HLA-DR expression and 35% had weak DR expression. We confirmed that patients with strong positive HLA-DR staining had improved survival (P<0.001) compared to patients with no HLA-DR expression. Strong epithelial HLA-DR staining was significantly associated with high level of microsatellite instability (P<0.001). In the subgroup of tumours with characteristics typical of the chromosomal instability phenotype, i.e. in microsatellite-stable tumours, the patients positive for the HLA-DR determinants showed better survival than those without HLA-DR expression. The protective effect of HLA-DR expression on survival was confirmed by multivariate analysis, both in the whole patient group and in the microsatellite-stable/microsatellite instability-low group. This might be explained by enhanced T-cell mediated anti-tumour immune responses against tumour cells in the HLA-DR positive tumours. The finding of better patient survival in the subgroup of strong HLA-DR positive microsatellite-stable tumours may have clinical implications for these patients