Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Despite the advances in pre-, peri- and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni- and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy.     

Cognitive task analysis: harmonizing tasks to human capacities

This paper presents the development of a cognitive task analysis that assesses the task load of jobs and provides indicators for the redesign of jobs. General principles of human task performance were selected and, subsequently, integrated into current task modelling techniques. The resulting cognitive task analysis centres around four aspects of task load: the number of actions in a period, the ratio between knowledge- and rule-based actions, lengthy uninterrupted actions, and momentary overloading. The method consists of three stages: (1) construction of a hierarchical task model, (2) a time-line analysis and task load assessment, and (3), if necessary, adjustment of the task model. An application of the cognitive task analysis in railway traffic control showed its benefits over the 'old' task load analysis of the Netherlands Railways. It provided a provisional standard for traffic control jobs, conveyed two load risks -- momentary overloading and underloading -- and resulted in proposals to satisfy the standard and to diminish the two load risk.     

Laparoscopic-assisted bowel resections in inflammatory bowel disease: state of the art

The objectives of this paper are to review the rational, the present results and future of laparoscopic-assisted bowel surgery in patients with inflammatory bowel disease (IBD). Only a few centres in the world report on laparoscopic bowel resection in IBD that include stoma surgery, ileocolic resection, left, right and (sub)total colectomy for Crohn's disease, and subtotal or restorative total proctocolectomy (ileal pouch anal procedures). The combined series report conversion rates between 2.5% and 22.2%. Ileocolic resection, stoma creation, stricturoplasty and segmental small bowel resection are associated with an acceptable length of surgery, but laparoscopic(-assisted) total colectomy or restorative proctocolectomy still demand up to 4-6 hours of operative time. The few randomised studies addressing laparoscopic-assisted (segmental) bowel surgery versus conventional surgery demonstrated significantly less pain, a quicker return to self-care and a shorter hospital stay. The results of the series reporting on laparoscopic-assisted (ileo)colectomy in IBD are similar to those from these randomised studies. Laparoscopic-assisted subtotal colectomy and restorative proctocolectomy have no benefit compared with conventional surgery other than superior cosmesis. Morbidity of laparoscopic (ileo)colectomy in IBD is low, that of laparoscopic-assisted subtotal colectomy and restorative proctocolectomy remains to be seen. The various laparoscopic bowel resections done in IBD are all feasible. The first series describing laparoscopic surgery for IBD indicate that laparoscopic-assisted segmental (ileo)colectomy is safe and is the preferred approach provided it is done in a centre specialised in the treatment of IBD and by skilled laparoscopic surgeons beyond the learning curve. Until now, laparoscopic-assisted subtotal colectomy and restorative proctocolectomy do not have the same short-term benefits as seen in other laparoscopic colorectal procedures. Patients with inflammatory bowel disease (IBD) have a high life-time risk of having abdominal surgery and reoperations. The proposed advantages of laparoscopic surgery in this group of young patients might be higher than in patients with other colorectal diseases. Minimal physiologic insult in patients who already are under significant physiologic stress, less adhesion formation and superior cosmesis are important benefits over time. In a time where patient's demands will increase, the future of laparoscopic colonic surgery in IBD looks assured.     

Effects of Cancer Presence and Therapy on the Platelet Proteome

Platelets are involved in tumor angiogenesis and cancer progression. Previous studies indicated that cancer could affect platelet content. In the current study, we investigated whether cancer-associated proteins can be discerned in the platelets of cancer patients, and whether antitumor treatment may affect the platelet proteome. Platelets were isolated from nine patients with different cancer types and ten healthy volunteers. From three patients, platelets were isolated before and after the start of antitumor treatment. Mass spectrometry-based proteomics of gel-fractionated platelet proteins were used to compare patients versus controls and before and after treatment initiation. A total of 4059 proteins were detected, of which 50 were significantly more abundant in patients, and 36 more in healthy volunteers. Eight of these proteins overlapped with our previous cancer platelet proteomics study. From these data, we selected potential biomarkers of cancer including six upregulated proteins (RNF213, CTSG, PGLYRP1, RPL8, S100A8, S100A9) and two downregulated proteins (GPX1, TNS1). Antitumor treatment resulted in increased levels of 432 proteins and decreased levels of 189 proteins. In conclusion, the platelet proteome may be affected in cancer patients and platelets are a potential source of cancer biomarkers. In addition, we found in a small group of patients that anticancer treatment significantly changes the platelet proteome.     

Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe

MRI detectable and targeted quantum dots were developed. To that aim, quantum dots were coated with paramagnetic and pegylated lipids, which resulted in a relaxivity, r(1), of nearly 2000 mM(-1)s(-1) per quantum dot. The quantum dots were functionalized by covalently linking alphavbeta3-specific RGD peptides, and the specificity was assessed and confirmed on cultured endothelial cells. The bimodal character, the high relaxivity, and the specificity of this nanoparticulate probe make it an excellent contrast agent for molecular imaging purposes.