Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area

Background: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. Methods: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. Results: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018). Conclusions: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment

Timing of nasogastric tube insertion and the risk of postoperative pneumonia: an international, prospective cohort study

Aim: Aspiration is a common cause of pneumonia in patients with postoperative ileus. Insertion of a nasogastric tube (NGT) is often performed, but this can be distressing. The aim of this study was to determine whether the timing of NGT insertion after surgery (before versus after vomiting) was associated with reduced rates of pneumonia in patients undergoing elective colorectal surgery. Method: This was a preplanned secondary analysis of a multicentre, prospective cohort study. Patients undergoing elective colorectal surgery between January 2018 and April 2018 were eligible. Those receiving a NGT were divided into three groups, based on the timing of the insertion: routine NGT (inserted at the time of surgery), prophylactic NGT (inserted after surgery but before vomiting) and reactive NGT (inserted after surgery and after vomiting). The primary outcome was the development of pneumonia within 30 days of surgery, which was compared between the prophylactic and reactive NGT groups using multivariable regression analysis. Results: A total of 4715 patients were included in the analysis and 1536 (32.6%) received a NGT. These were classified as routine in 926 (60.3%), reactive in 461 (30.0%) and prophylactic in 149 (9.7%). Two hundred patients (4.2%) developed pneumonia (no NGT 2.7%; routine NGT 5.2%; reactive NGT 10.6%; prophylactic NGT 11.4%). After adjustment for confounding factors, no significant difference in pneumonia rates was detected between the prophylactic and reactive NGT groups (odds ratio 1.03, 95% CI 0.56\u20131.87, P = 0.932). Conclusion: In patients who required the insertion of a NGT after surgery, prophylactic insertion was not associated with fewer cases of pneumonia within 30 days of surgery compared with reactive insertion