Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I(131) KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma.

BACKGROUND: Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy) provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I(131) in pancreatic cancer (ISRCTN 16857581). METHODS: Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death. RESULTS: Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33%) patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3).The overall response rate was 6% (1/18). Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months), with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79). One patient was still alive at the time of this analysis. CONCLUSION: Dose limiting toxicity for KAb201 with I(131) by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm.

Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma.

BACKGROUND: The objective of this study was to investigate whether the preoperative platelet-lymphocyte (P/L) ratio represents a significant prognostic index in resected pancreatic ductal adenocarcinoma. METHODS: A total of 110 patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma over a 10-year period were identified from a prospectively maintained database. RESULTS: The preoperative P/L ratio was found to be a more significant prognostic marker (P < .001) than either the lymphocyte count (P = .007) or platelet count (P = .068) on univariate Cox survival analysis. The median overall survival in patients with a P/L ratio of 150 or less (n = 48) was 19.7 months, 13.7 months in those with a P/L ratio of 151 to 300 (n = 43), and 5.8 months in patients with a value of greater than 300 (n = 19) (log-rank, P = .006). The preoperative P/L ratio retained significance on multivariate analysis (P < .001), along with tumor size (P = .010) and lymph node ratio (P = .013). CONCLUSIONS: The preoperative P/L ratio represents a significant independent prognostic index in patients of resected pancreatic adenocarcinoma.

The platelet-lymphocyte ratio improves the predictive value of serum CA19-9 levels in determining patient selection for staging laparoscopy in suspected periampullary cancer.

BACKGROUND: The objective of this study was to identify whether the preoperative platelet-lymphocyte (P/L) ratio might improve the predictive value of CA19-9 levels in stratifying a patient group with suspected periampullary malignancy who do not require staging laparoscopy. METHODS: Patients with suspected periampullary cancer were identified from a prospectively maintained 10-year database. Only patients with resectable disease who underwent staging laparoscopy and subsequent laparotomy were included. Low-risk groups were stratified using a CA19-9 cutoff value of < or = 150 kU/l (or < or = 300 kU/l in patients with a concurrent bilirubin concentration > 35 micromol/l) and a P/L ratio value of < or = 150. RESULTS: From 263 patients, preoperative CA19-9 levels and P/L ratios were available in 216 and 225 patients, respectively. The positive and negative predictive values for resectability, sensitivity, and specificity for CA19-9 levels < or = 150 kU/l were 83%, 36%, 51%, and 73%, respectively. For P/L ratios < or = 150, these levels were 81%, 38%, 51%, and 72%, respectively. When combining the requirement for both CA19-9 levels and P/L ratios to be < or = 150 (n = 38 out of 183), both positive predictive value (95%) and specificity (96%) were improved (Fisher exact test, P =.065 and P < .001, respectively); 21% of laparoscopies were avoidable when using these criteria. Increasing T stage (P = .005), vascular invasion (P < .001), perineural invasion (P = .008), and resection margin involvement (P < .001) were all associated with greater preoperative P/L ratios in resected periampullary adenocarcinoma (n = 204). CONCLUSIONS: The preoperative P/L ratio reflects an index of tumor invasiveness and merits prospective evaluation as an adjunct to CA19-9 in determining the requirement for laparoscopic staging in patients with potentially resectable periampullary malignancy.

Total parenteral nutrition: how to reduce the risks.

Total parenteral nutrition has a number of associated complications. These include air embolism and haemothorax on insertion of the line, infection, catheter blockage, catheter-related sepsis and thrombotic obstruction. A nurse-led initiative was undertaken to improve the administration of TPN through the development of evidence-based practice. The aims were to keep the catheter free from infection and blockage, with an uninterrupted feeding period, irrespective of length of time. A study of 235 episodes of feeding over two years showed a marked reduction in complications, and resulted in a dedicated unit for patients requiring TPN.