Circulating gelatinases and tissue inhibitor of metalloproteinase-1 in colorectal cancer metastatic liver disease.

AIMS: The degradation of the extracellular matrix is intrinsic to the invasion and progression of cancer. Matrix metalloproteinase (MMP)-2 and -9 and their natural inhibitors are involved in this process. The study aims to investigate if plasma MMP-2, -9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) can be useful markers in the diagnosis and prognosis of colorectal cancer (CRC) metastatic liver disease. METHODS: Fifty-seven patients undergoing liver metastasis operation were followed prospectively. ProMMP-2, -9 and TIMP-1 plasma levels were determined by zymography and ELISA, before and after the resection of liver metastases. Data were compared with those of healthy controls (n=51) and primary CRC patients (n=94). The diagnostic and prognostic potential was investigated with ROC-curves and Kaplan-Meier survival analysis. RESULTS: Plasma proMMP-2 levels were lower (P<0.001), and TIMP-1 levels higher (P<0.001) in CRC metastatic liver disease than in healthy controls. If compared to those in primary CRC patients, no differences were found. In ROC-curves, the area under the curve was 0.48 and 0.61 for proMMP-2 and -9, respectively. Plasma proMMP-2, -9 and TIMP-1 levels were unsuitable to predict survival. In both diagnostic and prognostic examinations, CEA proved to be a better marker. In the postoperative follow-up, protracted low levels of proMMP-2 seemed related to disease recurrence. CONCLUSION: The preoperative plasma proMMP-2, -9 and TIMP-1 levels have no potential value as diagnostic or prognostic markers in CRC liver metastatic disease.     

Reproducible marginal gap measurements of partial ceramic crowns

Aim of this research was to test the hypothesis that marginal gap measurements by a digital microscopic image processing computer are reproducible. Light microscopic images of the margins of Artglass partial crowns on stone dies were obtained with a 3CCD color video camera, digitized and processed. Ten measuring points were painted on a 0.5 mm section of the finish line of the preparation. The opposite corresponding measuring points on the margin of the partial crown were painted as well. The distance (marginal gap) between two corresponding points was painted and calculated by the computer. Reproducibility (precision) is reflected in the ability to reproduce the same measurement results in repeated measurements (n = 5). The reproducibility error was expressed as the coefficient of variation (CV) in percent (%). The localization of the corresponding measurement points and the calculation of the marginal gap were performed without errors. For a marginal gap between 15-50 microns the average measurement error was 3% or 0.45-1.5 microns. It was concluded that the measurement of the gap between two points by the digital image processing computer was reproducible. The measurement error was neglectable given that a clinically acceptable marginal gap is 100 microns.     

Jawbone reduction in immediate prostheses. A comparison between overdentures and complete dentures

In a randomized controlled clinical trial 74 patients who required immediate dentures were randomly treated with immediate overdentures on 2 lower canines or immediate complete dentures. Mandibular bone reduction was measured using oblique lateral cephalometric radiographs made at base-line and the results compared with those of one year and two years after denture treatment. Analysis of the data showed that the average bone reduction in the lower canine regions in the first year was 0.75 in the immediate overdenture group and 1.90 mm in the immediate complete denture group. In the posterior parts of the mandible the bone reduction was respectively 0.77 and 1.77 mm. The differences were statistically significant in all measured regions. The differences in the first two years were significant in all regions except the molar region. Retention of roots of canines beneath a mandibular denture in immediate denture patients, even when they were in poor condition, reduced the collapse of the alveolar processes in all region of the mandible.     

Osseointegrated Oral Implants in Head and Neck Cancer Patients

After cancer treatment in the head and neck area, mastication and speech are often affected. Some of the problems encountered can be solved by adequate dental rehabilitation. However, dental rehabilitation is often compromised for various reasons. The change in anatomy due to surgery often results in lack of denture-bearing mucosa. The effects of radiotherapy on the salivary glands and the mucosa result in dry oral tissue and diminished retention of removable dentures. Osseointegrated oral implants can help to solve these problems. Although implant treatment for patients with cancer of the head and neck is covered by the Dutch national health insurance, and there is therefore no financial obstacle, implants have not, so far, been widely used with these patients. In order to establish the possible reasons for this, an analysis was performed. Retrospective data on 95 consecutive patients were collected from records. The indication for the use of oral osseointegrated implants was reviewed. Analysis of the data showed that 45% did not need specific prosthetic rehabilitation. An indication for the use of osseointegrated implants was found in 25% of the patients. For various reasons, only 3% actually received implants. In striving to completely rehabilitate a cancer patient, the possible use of osseointegrated oral implants should be evaluated before the initial oncological treatment begins. The insertion of implants during the initial surgical procedure should be considered more often, with a view to reducing the number of surgical procedures.     

Novel Phase I dose de-escalation design trial to determine the biological modulatory dose of the antiangiogenic agent SU5416.

PURPOSE: To determine the biological modulatory dose of SU5416, we employed a novel trial design, where "dose de-escalation" was based on demonstrable biological changes observed at the maximum tolerated dose. If such an effect was shown, dose de-escalation to a predefined dose level would occur to determine if the lower dose exhibited the same amount of pharmacodynamic effect as the higher dose. EXPERIMENTAL DESIGN: Ten patients with advanced solid tumors were enrolled at each dose level. One of the following pharmacodynamic effects was considered significant: (a) a 35% decrease in microvessel density in sequential tumor biopsies and (b) a 35% decrease in blood flow within tumor as assessed by dynamic contrast-enhanced magnetic resonance imaging. In addition, soluble E-selectin, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, and plasma vascular endothelial growth factor were measured sequentially. RESULTS: Nineteen patients were enrolled. Sequential tumor biopsies in all evaluable patients showed an increase in microvessel density. Only one patient met the intended pharmacodynamic end point of >35% reduction in blood flow. There was a significant increase in both soluble E-selectin and soluble intercellular adhesion molecule levels pretreatment versus levels at the time of removal of patients from study (P = 0.04 and P = 0.0007, respectively). Levels of serum fibrinogen rose with therapy. There was a trend toward increase in plasma vascular endothelial growth factor levels. CONCLUSION: SU5416 does not result in decreased blood flow in tumors or a decrease in microvessel density. This corresponds to the lack of clinical activity seen with this agent. Our clinical trial design termed dose de-escalation is a novel approach to determine the in vivo biological effects of targeted therapies in cancer patients.     

Effectiveness of preparation guidelines for an all-ceramic restorative system

PURPOSE: To evaluate, in a clinical field-test, the implementation of manufacturer's preparation guidelines for the all-ceramic CICERO system. METHODS: General dental practitioners from the northwest region of The Netherlands were asked to make complete crown preparations in accordance with the specific guidelines of the CICERO system. 3,446 tooth preparations were evaluated with regard to shoulder angle, shoulder width and top angle. They were quantified using a special software program. The results were compared with criteria defined in the manufacturer's preparation guidelines. RESULTS: On a multivariate level all (main and interaction) effects were significant (P < 0.05) excluding the interaction effect of the location of measurement on the tooth by the upper or lower jaw. The value of the shoulder angle showed a strong relation with the tooth position in the mouth as well as with the location of measurement on the tooth. The shoulder width in the lower jaw was significantly smaller when compared to the width in the upper jaw. The shoulder width of the lower incisors was the smallest and also showed the largest variance per tooth. On a group level (incisor, cuspid, premolar, molar), except for the shoulder width of the lower incisors, the average values of all preparation parameters were within the borders as defined in the preparation guidelines of the manufacturer. However, on an individual tooth level nearly all preparations showed to have one or more locations with imperfections.     

Microbiological and clinical effects of chlorhexidine enclosed in fixtures of 3I-Titamed implants

This double-blind study used a split-mouth design to investigate the microbiological and clinical effects of 0.2% chlorhexidine enclosed in fixtures. Twelve patients had 46 fixtures implanted. At second-stage surgery, a microbiological sample (baseline sample) of the inner parts of the fixtures was taken. Then, a 0.2% chlorhexidine solution was applied into the inner space of 23 fixtures (test group), and in 23 fixtures saline was applied (control group). Abutments were installed and gingival index, plaque index and crevicular fluid flow were monitored weekly. After 6 weeks, a second microbiological sample of the inner part of the fixtures was taken. At baseline, viable bacteria were detected within 46% of the fixtures. After weeks, bacteria were found in 87% of the fixtures. The numbers of bacteria in the control group were significantly higher than those in the test group. The results indicate that, after first-stage surgery, contamination of the inner spaces of the fixtures is commonplace. Application of a 0.2% chlorhexidine solution at second-stage surgery inhibits growth or acquisition of bacteria in the fixtures. In both test and control groups, the crevicular fluid flow as well as the gingival index decreased during the experimental period. At 4, 5, and 6 weeks after chlorhexidine application, these values in the test group appeared lower, but did not attain statistical significance.     

Effect of GBR and fixture installation on gingiva and bone levels at adjacent teeth

Guided bone regeneration (GBR) is frequently used in oral implantology. It is unclear to what extent GBR affects the periodontium of adjacent teeth. Therefore, the present study quantifies changes in the proximal gingiva and bone levels at these teeth in 30 patients. Staged surgery involved a standard GBR treatment, randomly using resorbable membranes with a bone substitute or non-resorbable membranes with or without a bone substitute, followed by fixture installation at 6 months and abutment connection a further 6 months later. The data were sampled at each surgery and analysed using MANOVA. Twelve months after GBR, there was on average a small but statistically significant amount of proximal gingival recession (0.75 mm) and bone resorption (0.34 mm) observed, of which 50% was the result of GBR surgery. No significant differences were found between the different GBR treatment modalities. It is concluded that GBR treatment may have a small negative effect on the levels of the free gingival margin and alveolar bone at adjacent teeth, which is in most patients not clinically relevant.