Background Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status (chromosome-stable (CS) versus chromosomal instable (CIN)) remains unclear in gastric cancer. Methods Gene copy number aberrations (CNAs) were determined in 16 CIN-associated genes in a retrospective study including test and validation cohorts of patients with gastric cancer. Patients were stratified into CS (no CNA), CINlow (1-2 CNAs) or CINhigh (3 or more CNAs). The relationship between chromosomal status, clinicopathological variables, and overall survival (OS) was analysed. The relationship between chromosomal status, p53 expression, and tumour infiltrating immune cells was also assessed and validated externally. Results The test and validation cohorts included 206 and 748 patients, respectively. CINlow and CINhigh were seen in 35.0 and 15.0 per cent of patients, respectively, in the test cohort, and 48.5 and 20.7 per cent in the validation cohort. Patients with CINhigh gastric cancer had the poorest OS in the test and validation cohorts. In multivariable analysis, CINlow, CINhigh and pTNM stage III-IV (P < 0.001) were independently associated with poor OS. CIN was associated with high p53 expression and low immune cell infiltration. Conclusion CIN may be a potential new prognostic biomarker independent of pTNM stage in gastric cancer. Patients with gastric cancer demonstrating CIN appear to be immunosuppressed, which might represent one of the underlying mechanisms explaining the poor survival and may help guide future therapeutic decisions.

In this Management Issue, we present a website, www.apt.virtualpathology.leeds.ac.uk. While the website is entitled “Tips for Academic Pathology Trainees”, it contains information and advice which aims to be pertinent to those with and without academic aspirations. Specifically, it has been designed to a) promote a career in histopathology and b) support pathologists undertaking research, teaching or public engagement activities. The website represents a concise, comprehensive set of resources which has had 2000 visits since its launch in January 2019.

May 6, 2019April 9, 2019Free AccessThe Effect of Repetitive Head Impact Exposure on Response Inhibition in Contact Sport Athletes (P2.9-058)Kelsey Bryk, Alexander Wright, Jonathan D. Smirl, Michael Jakovac, and Paul Van DonkelaarAuthors Info & AffiliationsApril 9, 2019 issue92 (15_supplement)https://doi.org/10.1212/WNL.92.15_supplement.P2.9-058 Letters to the Editor

Abstract Ocular near point of convergence (NPC) has been shown to be sensitive to the effects of concussion and subconcussive impacts. To determine if NPC is also sensitive to a previous history of concussion, male contact-sport athletes either with (n=26) or without (n=16) a history of at least one previous concussion had their NPC assessed. The results showed that participants with a history of concussion displayed NPC values (9.4±1.6 cm) indistinguishable from those with no history of concussion (8.4±2.1 cm, t-test, p=0.09). This was the case regardless of whether 1, 2, or 3 or more concussions had occurred and despite the fact participants with concussion (mean time since last concussion: 1136 days) suffered from an increased number and severity of symptoms as assessed with the SCAT 3 (3.6±2.2 vs. 2.13±1.89 symptoms, 6.1±4.1 vs. 3.19±2.99 severity, t-test, p<0.05). Taken together, these results imply that NPC may not be a suitable tool to assess the potential long-term effects of one or more concussions over a longer time frame. Future research using larger sample sizes is warranted to evaluate the potential dose-response relationship between number of prior concussions and NPC.

Background: Vedolizumab is a humanised IgG monoclonal antibody that is licensed for use in moderate to severe ulcerative colitis and Crohn's disease. The manufacturer advises that vedolizumab is administered over thirty minutes, and that patients are observed for 2 hours after the first 2 infusions and for 1 hour after subsequent infusions for signs and symptoms of acute infusion related reactions. The aim of this audit was to establish whether monitoring following completion of the infusion is required. Methods: 179 Vedolizumab infusions were administered to 55 patients from November 2015 to July 2016 (9 months). Data was recorded on completion of the infusion and post infusion monitoring (PIM) period. Infusions were administered over 30 minutes. Patients were observed post infusion for 120 minutes following the first 2 doses, and 60 minutes after subsequent doses. Blood pressure, pulse, respiratory rate, oxygen saturations were recorded at the start and on completion of the infusion and hourly during post infusion monitoring. A systolic drop in BP of ≥20mm/Hg and details of action taken were documented. Adverse reactions, their treatment and outcomes were recorded, including occurrence during infusion or post infusion period. Adverse reactions were classified as: mild: no action required moderate: action required but treatment continued Severe: immediate action or treatment withdrawal. Results: During the infusion: 1 patient had an adverse reaction during each of 3 infusions (1 moderate, 2 mild). Systolic BP dropped ≥20mm/Hg in 3 patients (25–30mm/Hg). All patients were asymptomatic and infusions were completed as plan. During PIM: 1 patient did not comply with the PIM regime after their first infusion with no self-reported adverse events. 1 patient had a drop in systolic BP of 21mg/Hg following infusion 4 requiring no action. No adverse reactions were recorded in 55 patients following 178 infusions. 1 patient reported joint aches post discharge which settled spontaneously. Conclusions: Observed infusion reaction rate was 1.67% No adverse reactions occurred during post infusion monitoring. BP drops >20mm/Hg were observed in 1.67% infusions and 0.56% during post infusion monitoring. All patients were asymptomatic and no action was taken. We suggest post-vedolizumab infusion monitoring is unnecessary. In this Teaching Hospital setting, 347 hours of patient and nurse time could be saved per annum based on current infusion numbers.

Aims Histochemical staining of tissue is a fundamental technique in tissue diagnosis and research, but it suffers from significant variability. Efforts to address this include laboratory quality controls and quality assurance schemes, but these rely on subjective interpretation of stain quality, are laborious and have low reproducibility. We aimed (1) to develop a method for histochemical stain quantification using whole slide imaging and image analysis and (2) to demonstrate its usefulness in measuring staining variation.Methods A method to quantify the individual stain components of histochemical stains on virtual slides was developed. It was evaluated for repeatability and reproducibility, then applied to control sections of an appendix to quantify H&E staining (H/E intensities and H:E ratio) between automated staining machines and to measure differences between six regional diagnostic laboratories.Results The method was validated with <0.5% variation in H: E ratio measurement when using the same scanner for a batch of slides (ie, it was repeatable) but was not highly reproducible between scanners or over time, where variation of 7% was found. Application of the method showed H: E ratios between three staining machines varied from 0.69 to 0.93, H: E ratio variation over time was observed. Interlaboratory comparison demonstrated differences in H: E ratio between regional laboratories from 0.57 to 0.89.Conclusions A simple method using whole slide imaging can be used to quantify and compare histochemical staining. This method could be deployed in routine quality assurance and quality control. Work is needed on whole slide imaging devices to improve reproducibility.

The development of tamoxifen resistance (TR) in oestrogen-dependent breast cancer (BC) is a therapeutic challenge. Insulin-like growth factor binding proteins (IGFBPs) may play a role in this process. We have investigated the role of IGFBP proteins in TR BC. IGF axis genes were evaluated in MCF-7 (wt) cells and tamoxifen-resistant (TamR) variants using qRT-PCR and confirmed by ELISA, Western, and Ligand blotting. IGFBP-2 & -5 were knocked down by shRNA transfection, and subsequent sensitivity to 4-hydroxytamoxifen (4-HT) was determined via WST-1. Cell migration was investigated by using the Incucyte system. IGFBP-2 expression was evaluated in 424 BC cases by TMA immunohistochemistry. Five out of 10 genes of the IGF axis (IGF-IR, IGF-2R, IGFBP-2, -4 and -5) had the highest expression levels by both parental wt and TamR cells. IGFBP-5 was down-regulated by ~7-fold while IGFBP-2 was up-regulated by ~2-fold in TamR versus wt cells (mRNA and protein levels). Significantly, a knockdown of IGFBP-2 in TamR cells restored sensitivity to (4-HT), reduced ERα expression to 45 ± 11.9% and enhanced cell migration. Expression of IGFBP-2 was signicantly (P< 0.001) associated with survival advantage in TR patients. IGFBP-2 and IGFPB-5 are reciprocally regulated in the acquisition of TR by MCF-7 cells. IGFBP-2 may play a role in the development of TR in vitro and its high levels in clinical samples may predict TR.