Aims and Background. Patients in the United Kingdom with operable gastric and gastro-oesophageal junction (GOJ) tumours receive neoadjuvant chemotherapy. Our aim was to study the expression of thymidylate synthase (TS) enzyme in pre-treatment diagnostic biopsy specimens and investigate its clinical usefulness. Methods. A single-centre study was carried out in 45 patients with gastric and GOJ adenocarcinoma treated with neo-adjuvant chemotherapy according to the MAGIC protocol. TS expression was determined using immunohistochemistry. >10% tumour nuclei expression of TS was used as cut-off for positivity. Results. Forty-one (91%) of the 45 tumours expressed TS. There was no association between TS expression and lymph node status (P = 0.80), histological response (P = 0.30), and recurrence (P = 0.55). On univariate analysis, only N-stage (P = 0.02) and vascular invasion (P = 0.04) were associated with a poor prognosis. Patients with negative tumour TS expression had better outcome than those with positive expression. The overall 5-year survival rate was 100% in the TS negative versus 56% in TS positive group, but the difference was not statistically significant (P = 0.17). Conclusion. TS expression should be studied in a larger series of gastro-oesophageal cancers as a potential prognostic marker of prognosis to neo-adjuvant chemotherapy.

Department of Health Start Smart then Focus recommends that successful antimicrobial stewardship (AMS) programmes include a ward-focused antimicrobial team. Nurses are underutilised in AMS, and nurse/pharmacist-led initiatives have not been well described in the literature. A shortage of consultant microbiologists has required the AMS team to consider a creative multidisciplinary approach to post-prescription review and individual feedback at ward level. Discussion This project has demonstrated the value of a nurse/pharmacist collaboration for improving antimicrobial prescribing. The low intervention rate for IVOS was deemed to be due to the timing of intervention in relation to patient admission and has led to a change of focus to areas where duration of stay is typically longer. Future vision is to ensure sustainability in the context of long-term doctor shortages and continue to evidence the value of non-medical prescribers in AMS.

Background: Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy is becoming standard practice in the management of lung cancer. The expression of PD-L1protein is expected to apply to evaluate the prognosis or to predict the response to PD-1-blocking antibodies. The immunohistochemistry(IHC) assay forPD-L1, 22C3 pharmDx, has revealed that about30% of all non-small cell lung cancer (NSCLCs) express the PD-L1 with a high level. The association between PD-L1 positivity and the clinicopathological features in lung adenocarcinoma (ADC) remains unclear, however. Method: We retrospectively evaluated the PD-L1 expression in the surgically resected tumor tissues by IHC with the 22C3 assay, from 233 primary lung ADC patients. The PD-L1 tumor proportion score (TPS) was calculated as the percentage of at least 100 viable tumor cells with complete or partial membrane staining. TPS was reported in three categories (no expression, <1%; low expression, 1-49%; and high expression, 50%). Result: Of the 233 cases analyzed, the median age was 60 (range, 34-82 years), 149 (63.9%) patients were female, 167 (71.7%) patients were never-smokers, and 55 (23.6%) patients had stage Ⅲ (50) and Ⅳ (5) disease. Among them, 139 (59.7%) patients had activating EGFR mutations, and 23 (9.9%) patients were KRAS mutant. Proportions in each PD-L1 TPS category were: <1%, 63.9%(149/233); 1-49%, 23.6%(55/233); 50%, 12.5%(29/233). Wilcoxon rank sum test(Mann-Whitney U test) revealed that PD-L1 positivity had negative correlation with patient age (p ¼ 0.027), and positive correlation with male (p ¼ 0.001), smoker (p ¼ 0.007), advanced stage (p < 0.001). EGFR-mutated tumors (n¼ 139) demonstrated lower rates of PD-L1 expression [TPS <1% (72.7%); 1-49% (22.3%); 50% (5.0%); P<0.001];meanwhile, KRAS-mutated tumors (n¼ 23) showed higher rates of PD-L1 expression [TPS <1% (43.5%); 1-49% (30.4%); 50% (26.1%); P<0.001]. Conclusion: This investigation shows that in primary lung adenocarcinoma the PD-L1 expression was significantly associated with younger age, male, smokers, high stage disease, EGFR wild-type and KRAS mutant. Therefore, it is rational to choose a different checkpoint inhibitor according to the driver gene mutation status and to combine targeted therapies and anti-PD-L1 agents.Background: Four PD-L1 antibodies have been utilized in NSCLC clinical trials, with an analytical comparison demonstrating a high level of concordance between the percentage of PD-L1estained tumor cells with three of these antibodies (22C3, 22C3, 28-8, and SP263), but not a fourth, SP-142 (Hirsch et al, JTO 2017). This finding led us to evaluate the relationship between the percentage of PD-L1estained tumor cells with 22C3 and SP-142, as well as the association between the PD-L1 levels identified by each antibody and clinical outcomes in 28 NSCLC patients treated on KEYNOTE-001. Method: We performed a retrospective analysis of 28 NSCLC patients treated with pembrolizumab on the KEYNOTE-001 trial at UCLA (23pts) or MSKCC (5pts) with...

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Background: Small biopsy or cytology samples may present with a different level of PD-L1 expression compared to resected samples (which usually entail scoring of a much greater number of cells) resulting in relatively increased or reduced tumour proportion scores (TPSs). Many PD-L1 results are based on cytology fine needle lymph node aspirates (FNLNAs), encompassing analysis of metastatic disease and the substitution of cytology for histology samples. We compared the PD-L1 TPS of metastatic FNLNAs with that of resected non small cell carcinoma. Method: The pathology archive at Wythenshawe Hospital was searched for cases with adequate material over a period spanning 2010-2016. The Ventana SP263 PD-L1 clone was used to stain blocks select from 50 resected NSCCs and matched FNLNA cell blocks from each individual, along with a fresh H&E and negative PD-L1 control section. Result: Four of the cell block sections were inadequate for TPS assessment. The remaining 46 cases comprised 21 adenocarcinomas, 3 large cell carcinomas, 1 large cell neuroendocrine carcinoma, 1 atypical carcinoid tumour, and 20 squamous carcinomas. 34 cell block PD-L1 TPSs (68%) were in broad agreement with the corresponding resection block TPS, based on cutoff levels of 1% and 50%. Of the 12 (32%) cases in which differences occurred, 6 (50%) reflected an increase in TPS from resection to FNA, while 6 reflected a decrease causing a change in therapeutic cutoff. Nine of the FNLNAs were sampled after the resection, favouring the presence of recurrent disease. Conclusion: The majority of metastatic TPS FNLNAs are in broad agreement with a primary resected carcinoma TPS. FNLNAs tended to score less in the 1-49% category, possibly due to limits of cellularity. In addition to heterogeneity of expression, sampling of recurrent rather than residual disease may contribute to discrepancies.