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Uncontrolled endocrine pathology can cause significant adverse complications during a patient’s perioperative journey. With the ageing population, increasing co morbidity and rising obesity rates, the incidence of endocrine disease in elective and emergency work is likely to increase. A thorough understanding of diagnosis and management perioperatively is essential to prevent any excess morbidity and mortality. The perioperative period may precipitate endocrine emergencies which require rapid diagnosis and life-saving treatments. This article will cover the management of diabetes, thyroid and adrenal disease in the perioperative period.

The purpose of this study was to examine the effects of reductions in blood volume and associated oxygen-carrying capacity on the incidence of plateau at $$\dot{V}{\text{O}}$$ 2max. Fifteen well-trained athletes (age 23.3 ± 4.5; mass 77.4 ± 13.1 kg, height 180.1 ± 6.0 cm) completed three incremental cycle tests to volitional exhaustion, of which the first was defined as familiarisation, with the remaining two trials forming the experimental conditions of pre- (UBL) and post-(BLE) blood donation (~450 cm3). The work rate for the incremental tests commenced at 100 W for 60 s followed by a ramp of 0.42 W s−1, with cadence being held constant at 80 rpm. Throughout all trials, $$\dot{V}{\text{O}}$$ 2 was determined on a breath-by-breath basis using a pre-calibrated metabolic cart. The criteria for plateau determination was a ∆ $$\dot{V}{\text{O}}$$ 2 ≤ 50 ml min−1 over the final two consecutive 30 s sampling periods. Despite a significant (P = 0.0028) 9.4 % reduction in haemoglobin concentration and 10.8 % (P = 0.016) reduction in erythrocyte count between UBL and BLE, there was no change in plateau incidence. However, significant differences were observed for both $$\dot{V}{\text{O}}$$ 2max (P = 0.0059) 51.3 ± 7.6 (UBL) 48.4 ± 7.9 ml kg−1 min−1 (BLE) and gas exchange threshold arrival time 383.4 ± 85.2 s (UBL) 349.2 ± 71.4 s (BLE) (P = 0.0028). These data suggest that plateau at $$\dot{V}{\text{O}}$$ 2max is unaffected by O2 availability lending support to the notion of the plateau being dependent on the anaerobic capacity and the classically orientated concept of $$\dot{V}{\text{O}}$$ 2max.

Atypical teratoid rhabdoid tumours (AT / RT) are rare pediatric brain tumours characterised by bialleic loss of the SMARCB1 tumor suppressor gene. In contrast to pediatric AT / RT which has a simple genome, very little is known about the adult AT / RT genomic landscape. Using a combination of whole-exome sequencing and high-resolution SNP array in a single adult pituitary AT / RT we identified a total of 47 nonsynonymous mutations, of which 20 were predicted to cause nonconservative amino acid substitutions, in addition to a subclone of cells with trisomy 8. We suggest that adult AT / RT may not be markedly dissimilar to other adult brain tumors where mutations in a range of genes, reflecting the functional specialization of different brain regions, but including SMARCB1 inactivation, may be required for its pathogenesis.

Introduction Atypical teratoid rhabdoid tumors (AT/RT) are rare pediatric embryonal brain tumors. AT/RT are genomically characterized by a very simple genomic landscape caused by inactivation of the SMARCB1 tumor suppressor, chromatin remodelling, gene. Adult AT/RT is a super-rare disease with only 33 cases previously reported. For the first time, we report an adult pituitary AT/RT which has undergone whole-exome sequencing (WES) from a patient who subsequently died of intrachemotherapy leptomeningeal progression. Results In combination, the detection of both somatic biallelic SMARCB1 mutations and the loss of INI-1 protein expression confirmed the diagnosis of AT/RT. Trisomy 8 was detected in a minority of AT/RT cells. The overall somatic mutation rate was 1.9 Mb. A total of 98 somatic mutations were detected of which 20/49 non-synonymous coding mutations were predicted to be potentially damaging to protein function. These 20 genes were stratified into 4 functionally discrete groups: Group 1). tubulin / actin dynamics; Group 2). cell adhesion; Group 3). metabolism; Group 4). cytotoxic resistance mechanisms. Molecular pathway analysis predicted that loss of NOTCH1 signalling could be an important cellular node that was perturbed by a combination of LNX1 and POFUT1 mutations. AT/RT cells did not express any endocrine differentiation markers. Furthermore, 90% of AT/RT cells demonstrated intense nuclear p53 expression despite no TP53 mutations or HDM2 amplification being detected. Conclusions This is the first adult AT/RT to have undergone next-generation sequencing using WES. We have shown that the genomic landscape can be relatively complex in comparison to pediatric primary AT/RT(Lee RS et al 2012. J Clin Invest; 122(8):2983-2988). First, we detected a somatic mutation rate which was four times higher (1.9 Mb versus Given the dedifferentiated phenotype of AT/RT cells and that NOTCH1 signalling is known to be essential for maintaining the pituitary stem cell pool, we hypothesize that the combined effects of LNX1 and POFUT1 mutations could have been important events in the generation of an AT/RT cancer-initiating cell, through loss of NOTCH1 signalling. In this regard, we are currently investigating the expression of NOTCH1 signalling proteins, as well as elucidating the cause of the high levels of nuclear p53 expression within this AT/RT, which we also hypothesize was related to perturbations in NOTCH1 signalling. Note: This abstract was not presented at the meeting. Citation Format: Swethajit Biswas, Madeleine Wood, Abhijit Joshi, Nick Bown, Lisa Strain, Philip Kane, Tommy Martinsson, Javier Garrido, James Campbell, Amanda Swain, Alan Ashworth. Whole-exome sequencing of an adult pituitary atypical teratoid rhabdoid tumor (AT/RT) - A not so simple genome as pediatric AT/RT. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5082. doi:10.1158/1538-7445.AM2014-5082