Background: Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma.Methods: After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features.Results: CD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013).Conclusions: This study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma.

Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required.

Background: The aim of this study was to establish features of inflammation in histologically normal gallbladders with gallstones and compare the expression of inflammatory markers in acutely and chronically inflamed gallbladders.Methods: Immunohistochemistry was performed on formalin‐fixed paraffin‐embedded gallbladders for tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐2R, and substance p in three groups: Group I (n = 60) chronic cholecystitis, Group II (n = 57) acute cholecystitis and Group III (n = 45) histologically normal gallbladders with gallstones. Expression was quantified using the H‐scoring system.Results: Median, interquartile range expression of mucosal IL‐2R in Groups I (2.65, 0.87–7.97) and II (12.30, 6.15–25.55) was significantly increased compared with group III (0.40, 0.10–1.35, p < 0.05). Submucosal IL‐2R expression in Groups I (2.0, 1.12–4.95) and II (10.0, 5.95–14.30) was also significantly increased compared with Group III (0.50, 0.15–1.05, p < 0.05). There was no difference in the lymphoid cell IL‐6 expression between Groups I (5.95, 1.60–18.15), II (6.10, 1.1–36.15) and III (8.30, 2.60–26.35, p > 0.05). Epithelial IL‐6 expression of Group III (8.3, 2.6–26.3) was significantly increased compared with group I (0.5, 0–10.2, p < 0.05) as was epithelial TNF‐α expression in Group III (85.0, 70.50–92.0) compared with Groups I (72.50, 45.25.0–85.50, p < 0.05) and II (61.0, 30.0–92.0, p < 0.05). Lymphoid cell Substance P expression in Groups I (1.90, 1.32–2.65) and II (5.62, 2.50–20.8) was significantly increased compared with Group III (1.0,1.0–1.30, p < 0.05). Epithelial cell expression of Substance P in Group III (121.7, 94.6–167.8) was significantly increased compared with Groups I (75.7, 50.6–105.3, p < 0.05) and II (78.9, 43.5–118.5, p < 0.05).Conclusion: Histologically normal gallbladders with gallstones exhibited features of inflammation on immunohistochemistry.

Introduction: Painful symptomatic diverticular disease (SDD) is a common but poorly understood condition. Approximately 20% of patients with diverticulosis complain of pain, but there are currently no effective treatments. We have previously reported peripheral immune activation and alteration in colonic nerve function in SDD. Aims: To test the significance of this immune activation by performing the first parallel design, double blind, randomised placebo controlled trial of an anti-inflammatory drug, mesalazine in SDD. Methods: Patients with confirmed SDD underwent an unprepared flexible sigmoidoscopy and biopsies at baseline and after 12 weeks treatment, completing diaries of pain and bowel habit. They were randomised to receive 3 g per day of mesalazine (M) or identical placebo (P) for 12 weeks with follow-up visits at 2 & 4 weeks. RNA from sigmoid biopsies was analysed using a custom made gene card. Gene expression and changes in symptoms were assessed between baseline and final visits using Wilcoxon signed-rank test. Results: 43 volunteers were recruited (F:M; 24:19), but 11 withdrew during the study resulting in 18 and 14 participants in the P and M groups respectively. M significantly reduced important inflammatory and pain genes including those involved in response to bacterial ligands (Abstract OC-119 table 1), changes not seen with P. M but not P significantly reduced the duration of abdominal pain (Median (range) (hrs/day) P group Pre 1.0 (0–5), Post 0.65 (0–4) p0.1919; M Group Pre 3.0 (0–20), Post 0.125 (0–5.5) p0.0413). Abstract OC-119 Table 1 Relative quantity of inflammatory genes from SDD patients pre and post treatment with Placebo (P) or Mesalazine (M) (Median [inter-quartile range]) Median (IQR) P group p Value M group p Value Genes Pre Post Pre Post NOD2 0.8938 (0.76–1.57) 1.021 (0.60–1.55) 0.6632 1.359 (0.79–1.96) 0.5925 (0.40–0.94) 0.0002 PAR2 1.841 (1.40–2.34) 1.571 (1.20–2.08) 0.4080 1.944 (1.49–3.37) 1.056 (0.77–1.25) 0.0007 TNFα 0.6611 (0.47–1.05) 0.6341 (0.34–1.15) 0.2977 0.9170 (0.61–1.40) 0.4435 (0.36–0.69) 0.0034 IL1B 0.7416 (0.47–1.40) 1.092 (0.37–1.49) 0.2575 0.9633 (0.37–1.96) 0.6220 (0.37–1.01) 0.0024 TLR4 1.377 (0.94–2.49) 1.465 (1.05–1.94) 0.3604 1.537 (1.01–1.96) 0.8932 (0.70–1.52) 0.0479 TLR9 0.4506 (0.34–0.73) 0.5264 (0.30–0.68) 0.4488 0.7991 (0.39–1.17) 0.4976 (0.32–0.64) 0.0215 MYD88 1.765 (1.51–2.66) 1.678 (1.22–2.44) 0.6013 1.780 (1.15–2.99) 1.134 (0.90–1.76) 0.0105 Conclusion: This pilot study suggests that mesalazine significantly alters many of the pathways mediating immune activation by bacteria thought to contribute to pain in SDD and may provide benefit for patients. However further larger studies are required to confirm these mechanisms and efficacy of mesalazine in this group. Competing interests: J Smith grant/research support from: Wellcome Trust Training Fellowship, Conflict with: £17 000 Gift from Dr Falk Pharma for manufacture of medication for the study, D Humes: None declared, K Garsed: None declared, C Lam: None declared, A Zaitoun: None declared, A Bennett: None declared, J Scholefield: None declared, R Spiller: None declared.

Elevated serum concentrations of M2-pyruvate kinase (M2-PK) correlate with poor prognosis in patients with pancreaticobiliary and duodenal cancer, but the expression of M2-PK in formalin-fixed pancreatic tissue is unknown. We aimed to characterise the immunohistochemical expression of M2-PK in archived specimens of pancreaticobiliary and duodenal cancers, premalignant lesions, chronic pancreatitis, and normal pancreas.