The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis.

The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important characteristics that define the degree of cardiac remodeling in this model. A systematic review and meta-analyses were performed on studies using the TAC mouse/rat model and reporting echocardiographic outcome parameters. We included all animal studies in which a constriction around the transverse aorta and at least one of the predefined echocardiography or MRI outcome parameters were assessed. A total of 502 articles and > 3000 wild-type, untreated animals undergoing TAC were included in this study and referenced to a control group. The duration of aortic constriction correlated to the degree of adverse remodeling. However, the mouse data is strongly biased by the preferential use of male C57Bl/6 mice (66% of studies). Furthermore, mostly ketamine/xylazine anesthetics, 27G needle constriction, and silk sutures are used. Nonetheless, despite the homogeneity in experimental design, the model contained a substantial degree of heterogeneity in the functional outcome measures. When looking at study quality, only 12% reported randomization, 23% mentioned any sort of blinding, 25% adequately addressed the outcomes, and an amazingly low percentage (2%) showed sample size calculation. Meta-analyses did not detect specific study characteristics that explained the heterogeneity in the reported outcome measures, however this might be related to the strong bias towards the use of specific mouse lines, sex as well as age or to poor reporting of characteristics of study quality.

A study into methodology and application of quantification of tumour vasculature in rectal cancer.

The application of new surgical techniques in combination with preoperative radiotherapy has minimised the risk of local recurrence in rectal cancer. However, distant metastasis is still a serious problem after seemingly curative resection in patients with rectal cancer. The present study aimed to evaluate the methodology for quantification and the characteristics of the tumour vasculature in relation to the development of metastasis in patients with rectal cancer. From a large multicentre trial, 88 patients were selected, ensuring a relatively high percentage of metastasis. This selection facilitates the study of tumour vasculature characteristics in relation to metastasis. Vessel number, perimeter and area were assessed at both the invasive front and intratumoural area. Hot-spot and random selections were performed simultaneously. The median of each vessel parameter in the study population was used to separate patients into a low- and high-vessel group. Differences in development of distant metastasis were studied between low- and high-vessel groups. The data of the present study show that only vascular perimeter randomly assessed at the invasive front was associated with distant metastasis. Patients with a high score had a lower distant metastasis rate than patients with a low score (37% and 62%, respectively). High-vessel perimeter was independent of tumor node metastasis staging, but was associated with an increased presence of immune cells, comprising T cells, mast cells, eosinophils and neutrophils. This methodological study on the biological relevance of various vessel characteristics showed that a large vascular endothelial surface, as reflected by a high perimeter, was the only vessel characteristic indicative of improved patient outcome. The underlying principle for this association may be the improved immune response.

Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control.

PURPOSE: Quality assessment and assurance are important issues in modern health care. For the evaluation of surgical procedures, there are indirect parameters such as complication, recurrence, and survival rates. These parameters are of limited value for the individual surgeon, and there is an obvious need for direct parameters. We have evaluated criteria by which pathologists can judge the quality or completeness of the resection specimen in a randomized trial for rectal cancer. PATIENTS AND METHODS: The pathology reports of all patients entered onto a Dutch multicenter randomized trial were reviewed. All participating pathologists had been instructed by workshops and videos in order to obtain standardized pathology work-up. A three-tiered classification was applied to assess completeness of the total mesorectal excision (TME). Prognostic value of this classification was tested using log-rank analysis of Kaplan-Meier survival curves using the data of all patients who did not receive any adjuvant treatment. RESULTS: Included were 180 patients. In 24% (n = 43), the mesorectum was incomplete. Patients in this group had an increased risk for local and distant recurrence, 36.1% v. 20.3% recurrence in the group with a complete mesorectum (P =.02). Follow-up is too short to observe an effect on survival rates. CONCLUSION: A patient's prognosis is predicted by applying a classification of macroscopic completeness on a rectal resection specimen. We conclude that pathologists are able to judge the quality of TME for rectal cancer. With this direct interdisciplinary assessment instrument, we establish a new role of the pathologist in quality control.