Relationship between tumour size and outcome in pancreatic ductal adenocarcinoma.

BACKGROUND: The size of pancreatic ductal adenocarcinoma (PDAC) at diagnosis is an indicator of outcome. Previous studies have focused mostly on patients with resectable disease. The aim of this study was to investigate the relationship between tumour size and risk of metastasis and death in a large PDAC cohort, including all stages. METHODS: Patients diagnosed with PDAC between 1988 and 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Tumour size was defined as the maximum dimension of the tumour as provided by the registry. Metastatic spread was assessed, and survival was calculated according to size of the primary tumour using the Kaplan-Meier method. Cox proportional regression modelling was used to adjust for known confounders. RESULTS: Some 58 728 patients were included. There were 187 patients (0·3 per cent) with a tumour size of 0·5 cm or less, in whom the rate of distant metastasis was 30·6 per cent. The probability of tumour dissemination was associated with tumour size at the time of diagnosis. The association between survival and tumour size was linear for patients with localized tumours, but stochastic in patients with regional and distant stages. In patients with resected tumours, increasing tumour size was associated with worse tumour-specific survival, whereas size was not associated with survival in patients with unresected tumours. In the adjusted Cox regression analysis, the death rate increased by 4·1 per cent for each additional 1-cm increase in tumour size. CONCLUSION: Pancreatic cancer has a high metastatic capacity even in small tumours. The prognostic impact of tumour size is restricted to patients with localized disease.

In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.

The combination of two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.

Prevention of pleural adhesions by bioactive polypeptides - a pilot study.

OBJECTIVE: Postoperative pleural adhesions lead to major problems in repeated thoracic surgery. To date, no antiadhesive product has been proven clinically effective. Previous studies of differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG) have shown promising results reducing postoperative abdominal adhesions in experimental settings. This pilot study examined the possible pleural adhesion prevention by using the PL+PG concept after pleural surgery and its possible effect on key parameters; plasmin activator inhibitor-1 (PAI-1) and tissue growth factor beta 1 (TGFb) in the fibrinolytic process. METHODS: A total of 22 male rats were used in the study, one control group (n=10) and one experimental group (n=12). All animals underwent primary pleural surgery, the controls receiving saline in the pleural cavity and the experimental group the PL+PG solution administered by spray. The animals were evaluated on day 7. Macroscopic appearance of adhesions was evaluated by a scoring system. Histology slides of the adhesions and pleural biopsies for evaluation of PAI-1 and TGFb1 were taken on day 7. RESULTS: A significant reduction of adhesions in the PL+PG group (p<0.05) was noted at day 7 both regarding the length and severity of adhesions. There were no significant differences in the concentration of PAI-1 and TGFb1 when comparing the two groups. CONCLUSIONS: PL+PG may be used to prevent pleural adhesions. The process of fibrinolysis, and fibrosis was though not affected after PLPG administration.