Microvessel density predicts survival in prostate cancer patients subjected to watchful waiting.

The biological potential of prostate cancer is highly variable and cannot be satisfactorily predicted by histopathological criteria alone. Angiogenesis, the formation of new blood vessels, has been suggested to provide important prognostic information in prostate cancer. The aim of this study was to investigate whether microvessel density (MVD) at diagnosis was correlated with disease-specific survival in a non-curative treated population of prostate cancer patients. MVD was immunohistochemically (factor VIII-related antigen) quantified in archival tumours obtained at diagnosis in 221 prostate cancer patients. Median length of follow-up was 15 years. The maximal MVD was quantified inside a 0.25 mm2 area of the tumour and the median MVD was 43 (range 16-151) mm2. MVD was statistically significantly correlated with clinical stage (P < 0.0001) and histopathological grade (P < 0.0001). When dichotomized by the median counts, MVD was shown to be significantly associated (P = 0.0001) with disease-specific survival in the entire population as well as in the theoretically curable clinically localized subpopulation. A multivariate analysis demonstrated that MVD was a significant predictor of disease-specific survival in the entire cancer population (P = 0.0004), as well as in the clinically localized cancer population (P < 0.0001). These findings suggest that quantitation of angiogenesis reflects the spontaneous clinical outcome of prostate cancer.     

Patterns of angiogenesis in nonsmall-cell lung carcinoma

BACKGROUND: Tumor angiogenesis plays a pivotal role in tumor growth, maintenance, and metastasis. The objective of the current study was to evaluate the prognostic value of estimates of tumor angiogenesis and vascular endothelial growth factor (VEGF) status in 143 primary tumors from patients who underwent radical surgery for nonsmall-cell lung carcinoma (NSCLC). METHODS: Tumor sections were stained by immunohistochemistry for CD34 and VEGF. Angiogenesis was estimated both by a modification of the method described by Weidner and by the use of a 25-point Chalkley eyepiece graticule. VEGF intensity was evaluated semiquantitatively in three groups of patients. The vascular data were correlated with histopathologic tumor type and grade, TNM classification, patient age, and the endpoint (death). RESULTS: The estimates of vascular score did not reveal any prognostic information. In 35 patients (24%), invasive tumor growth was identified with a highly ordered alveolar microvessel pattern. In parallel sections, the intensity of VEGF staining was weak in tumors that exhibited an alveolar microvessel pattern only, and it was more intense in tumors that demonstrated a mixed alveolar and diffuse angiogenic pattern. The 35 patients with alveolar microvessel pattern had a significantly better survival (P = 0.007). In a Cox multivariate analysis, the results demonstrated an independent bad prognostic value of high disease stage (P < 0.0001), adenocarcinoma (P = 0.004), greater age (P = 0.01), and angiogenic microvessel pattern (P = 0.01). CONCLUSIONS: The authors believe that the alveolar vascular pattern represented preexisting alveolar vessels, that is, the alveoli were filled up by tumor cells that exploited the existing highly vascular bed of the lungs. Therefore, this subgroup was characterized by tumor progression without the induction of angiogenesis. The current data do not support a significant prognostic role for tumor angiogenesis in patients who are diagnosed with NSCLC. This may have implications for therapy aimed at inhibiting tumor growth by the inhibition of angiogenesis.     

Intense inflammation in bladder carcinoma is associated with angiogenesis and indicates good prognosis

The aim of this study was to investigate the prognostic influence of microvessel density using the hot spot method in 107 patients diagnosed with transitional cell carcinoma of the bladder. In each case, inflammation was found in the invasive carcinoma, therefore we classified the degree of inflammation as minimal, moderate or intense. Microvessel density was then reevaluated in each tumour in areas corresponding to these three categories. Median microvessel density irrespective of degree of inflammation was 71. Areas of minimal, moderate and intense inflammation were found in 48, 92 and 32 tumours. Microvessel density increased significantly with increasing degree of inflammation. Disease-specific survival was improved if areas of intense inflammation were present in the carcinoma (P=0.004). High microvessel density, irrespective of the degree of inflammation, was associated with a significantly better disease-specific survival (P=0.01). Multivariate analysis using death of disease as endpoint demonstrated an independent prognostic value of N-classification (N0, hazard ratio (HR)=1 vs N1, HR=2.89 (range, 1.52-5.52) vs N2, HR=3.61 (range, 1.84-7.08)), and intense inflammation, HR=0.48 (range, 0.24-0.96). Malignancy grade, T classification and microvessel density were not independent significant markers of poor outcome. In conclusion, inflammation was significantly correlated to microvessel density, and areas of intense inflammation were an independent marker of good prognosis.     

Inter-observer variation in delineation of the heart and left anterior descending coronary artery in radiotherapy for breast cancer: A multi-centre study from Denmark and the UK

Background and purpose

To determine the extent of inter-observer variation in delineation of the heart and left anterior descending coronary artery (LADCA) and its impact on estimated doses.

Methods and materials

Nine observers from five centres delineated the heart and LADCA on fifteen patients receiving left breast radiotherapy. The delineations were carried out twice, first without guidelines and then with a set of common guidelines.

Results

For the heart, most spatial variation in delineation was near the base of the heart whereas for the LADCA most variation was in its length at the apex of the heart. Common guidelines reduced the spatial variation for the heart and the length of the LAD, but increased the variation in the anterior–posterior/right–left plane. The coefficients of variation (CV) in the estimated doses to the heart were: mean dose 7.5% without and 3.6% with guidelines, maximum dose 8.7% without and 4.0% with guidelines. The CVs in the estimated doses to the LADCA were: mean dose 27% without and 29% with guidelines, maximum dose 39% without and 31% with guidelines.

Conclusions

For the heart, there was little inter-observer variation in the estimated dose, especially when guidelines were used. In contrast, for the LADCA there was substantial variation in the estimated dose, which was not reduced with guidelines.     

Morphological and topographical anatomy of nutrient foramina in the lower limb long bones and its clinical importance

Background

Knowledge regarding nutrient foramina of bones is useful in surgical procedures such as microvascular bone transfer in order to preserve the circulation. The objective of the present study was to study the morphology and topography of nutrient foramina and to determine the foraminal index of the lower limb long bones to provide detailed data on such features.

Method

The study comprised examination of 206 lower limb long bones which included femora, tibiae and fibulae. The nutrient foramina were identified analysed macroscopically and the foramen index calculated. Each bone was divided into five parts and topographical analysis was performed on each section.

Results

Femora had single nutrient foramen in 47.7% of the cases, double foramen in 44.2% of the cases, triple in 3.5% of the cases and an absence of foramen in 4.6%. In the case of tibiae, 98.6% showed single foramen and in 1.4% of the cases, the foramen was absent. With respect to fibulae, 90.2% had single foramen and foramen was absent in 9.8%. The mean foraminal index was 38.9 for the femora, 32.5 for tibiae and 49.2 for fibulae. The majority (51.3%) of the foramina in the femora were located at the 2/5^th part, 98.3% of the tibiae foramina at the 2/5^th part and 60% of the fibulae at the 3/5^th part.

Conclusion

The study provides information on the morphology and topography of nutrient foramina in lower limb long bones. The double foramina were more common in femur and rare in the tibia and fibula. The foramina of the femur and tibia were commonly observed at their upper part, whereas in the fibula they were present on the lower part. This knowledge of the nutrient foramina has to be kept in mind during surgical procedures.