Review on Factors Influencing Physician Guideline Adherence in Cardiology.

Cardiovascular disease is the most common cause of death in Western countries. Physician adherence to guidelines is often suboptimal, resulting in impaired patient outcome and prognosis. Multiple studies have been conducted to evaluate patterns and the influencing factors of patient adherence, but little is known about factors influencing physician guideline adherence. This review aims to identify factors influencing physician guideline adherence relevant to cardiology and to provide insights and suggestions for future improvement. Physician adherence was measured as adherence to standard local medical practice and applicable guidelines. Female gender and older age had a negative effect on physician guideline adherence. In addition, independent of the type of heart disease, physicians without cardiologic specialization were linked to physician noncompliance. Also, guideline adherence in primary care centers was at a lower level compared with secondary or tertiary care centers. The importance of guideline adherence increases as patients age, and complex diseases and comorbidity arise. Appropriate resources and interventions, taking important factors for nonadherence in account, are necessary to improve guideline adoption and adherence in every level of the chain. This in turn should improve patient outcome.

Comparison of ultrasound guidance with palpation and direct visualisation for peripheral vein cannulation in adult patients: a systematic review and meta-analysis.

BACKGROUND: Peripheral vein cannulation is a routine and straightforward invasive procedure, although i.v. access can be difficult to obtain. To increase the success rate of inserting an i.v. catheter, many devices have been proposed, including ultrasonography. The objective of this study was to compare ultrasound guidance with the traditional approach of palpation and direct visualisation for peripehral vein cannulation. The primary outcome was successful peripheral i.v. cannulation. METHODS: Database search was performed on PubMed, Clinical Key, CINAHL, Cochrane Library of Clinical Trials, and Trip Database (from January 2000 to December 2017). Random-effect meta-analysis was performed to determine the pooled odds ratio for success in peripheral i.v. cannulation. RESULTS: After database review and eligibility screening, eight studies were included in the final analysis, with a total of 1660 patients. The success rate in the ultrasound group was 81% (n=855), and was 70% (n=805) in the control group, resulting in a pooled odds ratio for success upon ultrasound-guided peripheral i.v. cannulation of 2.49 (95% confidence interval 1.37-4.52, P=0.003). Furthermore, the ultrasound-guided technique reduced the number of punctures and time needed to achieve i.v. access, and increased the level of patient satisfaction, although it did not result in a decreased number of complications. CONCLUSIONS: Ultrasound guidance increases the success rate of peripheral i.v. cannulation, especially in patients with known or predicted difficult i.v. access.

Determination of tumour prognosis based on angiogenesis-related vascular patterns measured by fractal and syntactic structure analysis.

AIMS: Intratumoural micro-vessel density (IMD) has recently been shown to be a valuable prognostic tool in many tumours. Yet, IMD does not take into account the spatial arrangement of the vessels, therefore only partly reflecting the angiogenic situation. In order to describe contextual vascular relationships more accurately, we have used fractal and syntactic structure analysis (SSA) based on computerised image processing to quantify micro-vascular hot spots. MATERIALS AND METHODS: The parametric performance in prediction of patients' outcome was evaluated by univariate analysis and compared with manually obtained IMDs, whereas an automated K-nearest-neighbour (KNN) classifier searched most discriminative parametric combinations. The method is based on analysis of vascular 'hot-spots' of paraffin-embedded tissue sections of invasive cervical carcinoma, colorectal carcinoma and malignant mesothelioma. RESULTS: For all three cancers, prediction of prognosis based on SSA yielded in general much higher recognition scores compared with IMD or fractal dimension. Survival of cervical carcinoma was mostly correlated with clinical data, with the vascular permeation being the only parameter with independent value. Prognosis of colorectal carcinoma is best described by SSA, completed with IMD, indicating an inverse correlation of survival time with a more irregular pattern and a slight increase in vessel number. For mesothelioma, we found a strong correlation with SSA and patients' outcome, with two SSA-parameters having independent prognostic value. CONCLUSIONS: The more accurate angiogenic description obtained with SSA may be useful for further exploitation as a prognosticator in a general diagnostic pathology service.

Transcontinental communication and quantitative digital histopathology via the Internet; with special reference to prostate neoplasia.

OBJECTIVE: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. MATERIALS: Experiences derived from medium power (sampling density 2.4 pixels/microm) and high power (6 pixels/microm) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. RESULTS: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. CONCLUSIONS: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.

Proliferation, DNA ploidy, p53 overexpression and nuclear DNA fragmentation in six equine melanocytic tumours.

Melanocytic tumours are a well-known clinical and pathological entity in horses, but further phenotypic characterization of these tumours is lacking. Six melanocytic tumours from five horses (two metastatic and four benign) were examined by Ki67, PCNA and p53 immunostaining, DNA nick end labelling (Tunel) and Feulgen staining. The stainings were evaluated using quantitative image analysis. The resulting parameters of growth fraction (Ki67), S-phase index (PCNA), p53 index, apoptotic index, DNA index, nuclear diameter, ploidy balance, proliferation index (Feulgen) and hyperploidy were analysed. The metastatic melanomas showed overexpression of p53 in a large portion of the cells. Apoptosis was also found in the metastatic melanomas. No differences were found in growth fraction, S-phase index (PCNA) nor in DNA configuration between the metastatic and the benign tumours. No immunohistochemical evidence of mutant p53 could be found in the tumours. In conclusion, melanocytic tumours in horses seem to have different phenotypic characteristics in comparison with melanocytic tumours in dogs, cats and humans, especially with respect to proliferative activity of the benign tumours. Therefore, markers put forward in these other species for predicting the clinical behaviour of the melanomas seem to be of no value in the horse. Moreover, quantitative DNA changes or p53 mutations do not seem to be involved in tumourogenesis in these cases.

Validation of nuclear texture, density, morphometry and tissue syntactic structure analysis as prognosticators of cervical carcinoma.

OBJECTIVE: To evaluate the performance of karyometry and histometry in the prediction of survival, recurrence and response of early-stage invasive cervical carcinoma. STUDY DESIGN: Nuclear morphometry, chromatin texture and tissue architecture (characterized by syntactic structure analysis) were measured using a semiautomated image analysis system on 46 cases of Feulgen-stained tissue sections. The performance of the features was compared to that of clinical features, reported to be the best prognosticators until now, such as age, lympho-vascular permeation, histologic type, stage and grade. A K nearest neighbor classifier was used for classification. RESULTS: In the prediction of three-year survival, recurrence and response, syntactic structure analysis proved to be the best performer. Classification rates were, respectively, 100%, 94.4% and 94.5%. In all classifications, karyometric and histometric features outperformed clinical features. In general, the best performing features described differences in second-order population statistics (standard deviations). CONCLUSION: The results show that a quantitative analysis based on nuclear morphology, chromatin texture and histology can be considered an excellent aid in the prognosis of invasive cervical carcinoma. The measurements are not hampered by the need to undertake complete resections and are suited to daily practice when implemented in a semiautomated image analysis system.

The association between vascular endothelial growth factor, microvessel density and clinicopathological features in invasive cervical cancer.

OBJECTIVE: The aim of this study was to analyse the vascular endothelial growth factor (VEGF) expression in a series of cervical carcinomas and to compare the results with the microvessel density (MVD) and clinicopathological features. STUDY DESIGN: The immunoreactivity for VEGF was studied in 130 invasive cervical carcinomas and in 22 patients with a carcinoma in situ of the cervix. The results were compared with the MVD. RESULTS: Staining for VEGF of less then 50% per slide occurred in 80% of the invasive carcinomas and in 82% of the in situ carcinomas. The median MVD was 261 vv/mm(2) (range: 11-1000) in the invasive group and 146 vv/mm(2) (range: 25-536) in the in situ group. Unlike the microvessel density there was no association between VEGF expression and survival. The MVD was higher in VEGF poorer (<50%) tumours (P=0.055). Beside tumour histology (P=0.012) there were no other significant relationships between the remaining histopathological findings and VEGF expression. CONCLUSION: Tissue VEGF expression has no prognostic value in contrast with the MVD in patients with invasive cervical cancer.

Data representation and reduction for chromatin texture in nuclei from premalignant prostatic, esophageal, and colonic lesions.

BACKGROUND: To identify nuclei and lesions with great specificity, a large set of karyometric features is arranged in the form of a linear profile, called a nuclear signature. The karyometric feature values are normalized as z-values. Their ordering along the profile axis is arbitrary but consistent. The profile of the nuclear signature is distinctive; it can be characterized by a new set of variables called contour features. A number of data reduction methods are introduced and their performance is compared with that of the karyometric features in the classification of prostatic, colonic, and esophageal lesions. METHODS: Contour characteristics were reduced to descriptive statistics of the set of z-values in the nuclear signature and to sequence information. The contour features derived were (1) relative frequencies of occurrence of z-values and of their differences and (2) co-occurrence statistics, run lengths of z-values, and statistics of higher-order dependencies. Performance was evaluated by comparing classification scores of diagnostic groups. RESULTS: Rates for correct classification by karyometric features alone and contour features alone indicate equivalent performance. Classification by a combined set of features led to an increase in correct classification. CONCLUSIONS: Image analysis and subsequent data reduction of nuclear signatures of contour features is a novel method, providing quantitative information that may lead to an effective identification of nuclei and lesions.

DNA ploidy and nuclear morphometric variables for the evaluation of melanocytic tumors in dogs and cats.

OBJECTIVE: To determine the prognostic importance of the DNA content and nuclear morphometric variables in melanocytic tumors of cats and dogs. SAMPLE POPULATION: 27 melanocytic tumors of dogs and cats. PROCEDURES: Biopsy specimens were investigated by quantitative image analysis after the Feulgen staining method. The DNA content (index), nuclear diameter, ploidy balance, proliferation index, hyperploidy, and growth fraction (Ki67) were measured. Using 1-way ANOVA and a Pearson correlation test, the relationships between the different variables were tested. Their role in the prognosis in affected dogs and cats was estimated using the Cox regression test with respect to 6 months postoperative survival rate. RESULTS: Significant correlations were found between DNA index and ploidy balance and proliferation index. A significant correlation was also found between hyperploidy and DNA index, and between ploidy balance and proliferation index. Significant differences were found between histologically malignant and benign melanocytic tumors but not between primary malignant tumors and metastatic malignant tumors for DNA index and ploidy balance. No correlation was found between DNA variables and survival time. CONCLUSION AND CLINICAL RELEVANCE: In melanocytic tumors of cats and dogs, DNA index and ploidy balance can be used to differentiate histologically benign from malignant tumors. However, DNA content and nuclear morphometric variables have little value in predicting survival time. The DNA index and ploidy balance provide an additional tool to evaluate melanocytic tumors of cats and dogs. Survival in dogs and cats with melanocytic tumors, however, is not determined by modifications of DNA content or changes in nuclear morphometry of tumor cells.

Fibrous intimal thickening at implantation as a risk factor for the outcome of cadaveric renal allografts.

BACKGROUND: During the past decade, the donor age of cadaveric renal allografts steadily increased. Because cerebrovascular injury is the main cause of death in this donor population, an increased prevalence of atherosclerotic lesions in the retrieved grafts could be anticipated. In a prospective study, we investigated the predictive value of morphologic lesions at implantation for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years. METHODS: In 50 consecutive adult recipients of a cadaveric renal allograft, under cyclosporine-based regimen, implantation biopsies and subsequent protocol biopsies at 18 months were performed, and morphometrically analyzed for the extent of glomerulosclerosis, interstitial fibrosis, and atherosclerosis. Risk factors were assessed at implantation and during the subsequent observation period of 18 months. Endpoints for this study were: the 24-hr creatinine clearance (normalized for body surface area) and the fractional interstitial volume at 1 1/2 years. RESULTS: In multivariate analysis, fibrous intimal thickening at implantation (FIT) was the main determinant of the functional and morphologic outcome at 1 1/2 years. FIT represented a relative risk of 4.55 for interstitial fibrosis (95% CI=1.855-11.138), and 1.89 for impaired renal function (95% CI=1.185-3.007) at 1 1/2 years. FIT adversely affected fractional interstitial volume at 1 1/2 years (34.3 vs. 27.7%, P=0.004), as well as renal function (54 vs. 68 ml/min/1.73 m2, P=0.028). CONCLUSIONS: Fibrous intimal thickening at implantation is a determinant risk factor for the functional and morphologic outcome of cadaveric renal allografts at 1 1/2 years.

Quantum groups with invariant integrals.

Quantum groups have been studied intensively for the last two decades from various points of view. The underlying mathematical structure is that of an algebra with a coproduct. Compact quantum groups admit Haar measures. However, if we want to have a Haar measure also in the noncompact case, we are forced to work with algebras without identity, and the notion of a coproduct has to be adapted. These considerations lead to the theory of multiplier Hopf algebras, which provides the mathematical tool for studying noncompact quantum groups with Haar measures. I will concentrate on the *-algebra case and assume positivity of the invariant integral. Doing so, I create an algebraic framework that serves as a model for the operator algebra approach to quantum groups. Indeed, the theory of locally compact quantum groups can be seen as the topological version of the theory of quantum groups as they are developed here in a purely algebraic context.

Computer-assisted differential diagnosis of malignant mesothelioma based on syntactic structure analysis.

BACKGROUND: Malignant mesothelioma, a mesoderm-derived tumor, is related to asbestos exposure and remains a diagnostic challenge because none of the genetic or immunohistochemical markers have yet been proven to be specific. To assist in the identification of mesothelioma and to differentiate it from other common lesions at the same location, we have tested the performance of syntactic structure analysis (SSA) in an automated classification procedure. MATERIALS AND METHODS: Light-microscopic images of tissue sections of malignant mesothelioma, hyperplastic mesothelium, and adenocarcinoma were analyzed using parameters selected from the Voronoi diagram, Gabriel's graph, and the minimum spanning tree which were classified with a K-nearest-neighbor algorithm. RESULTS: Results showed that mesotheliomas were diagnosed correctly in 74% of the cases; 76% of the adenocarcinomas were correctly graded, and 88% of the mesotheliomas were correctly typed. The performance of the parameters was dependent on the obtained classification (i.e., tumor-tumor versus tumor-benign). CONCLUSIONS: Our results suggest that SSA is valuable in the differential classification of mesothelioma and that it supplements a visually appraised diagnosis. The recognition scores may be increased by a combination of SSA with, for example, cellular or nuclear parameters, measured at higher magnifications to form a solid base for fully automated expert systems.

Angiogenesis in cervical intraepithelial neoplasia and the risk of recurrence.

OBJECTIVE: We sought to investigate whether angiogenesis can predict the risk of recurrence of cervical intraepithelial neoplasia after treatment. STUDY DESIGN: Microvessel density was studied in 75 patients with grade 3 cervical intraepithelial neoplasia and in 20 patients with microinvasive squamous carcinoma (International Federation of Gynecology and Obstetrics stage IA1) of the uterine cervix by staining representative tissue sections with the specific endothelial marker anti-CD31. The microvessel density was determined with a digital image analyzer. The results were correlated with clinical and histopathologic data. RESULTS: The mean vessel density was 264 per field (range, 86-674 per field) in grade 3 cervical intraepithelial neoplasia and 378 per field (range, 161-848 per field; P = .001) in microinvasive squamous carcinoma. Thirteen patients with grade 3 cervical intraepithelial neoplasia had recurrent cervical intraepithelial neoplasia (microvessel density, recurrent vs nonrecurrent; not significant). Multiple regression analysis in the noninvasive group confirmed that the mean vessel density (P = .121) had no prognostic value. Furthermore, it showed that the age at diagnosis (P = .011), menopausal status (P = .052), and treatment modality (P = .022) proved to be independent prognostic factors for recurrence. CONCLUSIONS: During the progression from noninvasive to microinvasive cervical carcinoma, the microvessel density increases significantly. However, the vessel density does not predict recurrence of noninvasive lesions.

Value of morphometry, texture analysis, densitometry, and histometry in the differential diagnosis and prognosis of malignant mesothelioma.

Malignant mesothelioma is a tumour with increasing incidence due to widespread use of its causative agent, asbestos, in the past decades. The poor survival necessitates a correct differentiation from other lesions at the same site, such as hyperplastic mesothelium and carcinomas metastatic to pleura or peritoneum. Since genetic and immunohistochemical markers are not absolutely differentiating, the diagnosis is based on the histology complemented with (immuno)histochemistry. However, as the tumour presents itself in numerous heterogeneous histological forms, visual evaluation is extremely difficult. In order to evaluate the prognostic and diagnostic performance of syntactic structure analysis (SSA), chromatin texture analysis, densitometry, and morphometry, an automated KNN-classification system has been used to compare Feulgen-stained tissue sections of hyperplastic mesothelium, malignant mesothelioma, and pulmonary adenocarcinoma. In addition, we also studied most discriminative aspects in the differentiation, typing, and prediction of survival. The results indicate that for the diagnosis of malignant mesothelioma, chromatin texture parameters outperform SSA, densitometry, and morphometry (recognition score=96.8 per cent). Most discriminative parameters highlight spatial patterns of the chromatin distribution that are hard to appraise visually and directly show the benefits of a quantitative approach. Typing of the tumour is best described by SSA parameters, relating to the spatial arrangement of the cells in the tissue (recognition score=94.9 per cent). In survival time classifications, chromatin texture yields the highest recognition score (82.9 per cent), although accurate estimations are unreliable due to a large degree of misclassification.

Combined characterization of composite tabular silver halide microcrystals by cryo-EFTEM/EELS and cryo-STEM/EDX techniques.

The combination of cryo-energy filtering transmission electron microscopy (EFTEM)/electron spectroscopic diffraction (ESD)/electron energy-loss spectroscopy (EELS) and cryo-energy-dispersive X-ray (EDX) analysis in the scanning transmission (STEM) and scanning (SEM) modes was applied for the characterization of composite tabular Ag(Br,I) microcrystals. A low-loss fine structure in EEL spectra between 4 and 26 eV was attributed to excitons and plasmons possibly superimposed with interband transitions and many-electron effects. The contrast tuning under the energy-filtering in the low-loss region was used to image the crystal morphology, defect structure (random dislocations and ¿111¿ stacking faults) and bend and edge contours as well as electron excitations in the microcrystals. Sharp extra reflections at commensurate positions in between the main Bragg reflections and diffuse honeycomb contours in ESD patterns of the microcrystals taken near the [111] zone were assigned to the number of defects in the shell region parallel to the grain edges and polyhedral clusters of interstitial silver cations, respectively. The imaginary part of the energy-loss function, Im (-1/epsilon), and the real and imaginary parts, epsilon1 and epsilon2, of the dielectric permittivity were determined by means of a Kramers-Kronig analysis. An assignment of exciton peaks based on calculations of electronic band structure of silver bromide is proposed. Inner-shell excitation bands of silver halide were detected in line with EDX-analyses. The energy-loss near-edge structure (ELNES) of the AgM4,5-edge governed by spin-orbital splitting between the 3d3/2- and 3d5/2-states has been evaluated. Combined silver and halide distributions were obtained by a three-window method (EFTEM) and by EDX/STEM including area mapping and line profiling of iodide.

Automated breast tumor diagnosis and grading based on wavelet chromatin texture description.

In this paper, wavelets were employed for multi-scale image analysis to extract parameters for the description of chromatin texture in the cytological diagnosis and grading of invasive breast cancer. Their value was estimated by comparing the performance of co-occurrence, densitometric, and morphometric parameters in an automated K-nearest neighbor (Knn) classification scheme based on light microscopic images of isolated nuclei of paraffin-embedded tissue. This design allowed a multifaceted cytological retrospective study of which the practical value can be judged easily. Results show that wavelets perform excellently with classification scores comparable with densitometric and co-occurrence features. Moreover, because wavelets showed a high additive value with the other textural groups, this panel allowed a very profound description with higher recognition scores than previously reported (76% for individual nuclei, 100% for cases). Morphometric parameters performed less well and only slightly increased correct classification. The major drawback, besides image segmentation errors demanding operator supervision, emanated to be the few false-negative cases, which restrict the immediate practical use. However, an enlargement of the parameter set may avoid this misclassification, resulting in an applicable expert system of practical use.

Quantification and prognostic relevance of angiogenic parameters in invasive cervical cancer.

Tumour stromal neovascularization was investigated in 114 invasive and 20 in situ carcinomas of the uterine cervix by staining representative sections with the specific endothelial marker anti CD31 (clone JC/70A, isotope IgG1). A digital image analyser was used to measure the immunoreactivity. The following parameters were determined in the 'hot spots': vessel counts, vessel perimeter and endothelial stained area (expressed per mm2). The results were correlated with clinical and histopathological data. There was no significant relationship between the histopathological findings (tumour histology, tumour differentiation, FIGO stage, presence of lymph node metastasis or lymphovascular space involvement) and the median vessel count. In a univariate analysis all angiogenesis parameters had prognostic value: a higher vascularity was associated with worse prognosis (P < 0.05). Multiple regression analysis showed that vascular permeation (P < 0.001) and the median vessel count (P = 0.005) were the most important prognostic indicators. In the future these criteria may be used for selection of patients for anti-angiogenesis therapy.

Biochemical and histopathological changes in nephrectomized mice.

Renal failure is characterized by the retention of nitrogenous metabolites such as urea, creatinine (CTN) and other guanidino compounds (GCs), uric acid, and hippuric acid, which could be related to the clinical syndrome associated with renal insufficiency. A model of renal failure has been developed in male C57BL x Swiss-Webster mice using nephrectomy (NX) and/or arterial ligation. A sham group (group A) and two nephrectomized groups, group B (one kidney removed) and group C (one kidney removed and ligation of the contralateral anterior artery branch), were studied. Ten days postsurgery, morphological and functional indices of renal failure were investigated. Nephrectomized mice manifested features of renal failure like polyuria and wasting. CTN clearance (CTN[Cl]) decreased by +/-26% in group B and +/-33% in group C as compared with the control values. Marked increases in the plasma concentration of guanidinosuccinic acid ([GSA] fourfold) and guanidine ([G] twofold) were observed in the experimental animals. CTN and alpha-keto-delta-guanidinovaleric acid (alpha-keto-delta-GVA) reached levels of, respectively, 1.5-fold and twofold those of controls. Urinary GSA excretion increased and guanidinoacetic acid (GAA) excretion decreased about twofold in group C. GSA increases (2.6-fold) were also observed in the brain in group C, in addition to a significant increase of G (2.5-fold) and gamma-guanidinobutyric acid ([GBA] 1.5-fold). Finally, the extent of NX was found to be 45.2% in group B and 71.4% in group C. Light microscopy revealed an expansion and increase in cellularity of the mesangium of the glomeruli, particularly in group C. A significant correlation (r = .574, P < .0001) was found between CTN(Cl) and the degree of NX as calculated from the remaining functional area. These data suggest that the model can be used as a tool for further pathophysiological and/or behavioral investigations of renal failure.

Evaluation of tumour angiogenesis as a prognostic marker in malignant mesothelioma.

Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumours. Malignant mesothelioma (MM) of the pleura is a highly invasive tumour with a poor prognosis. In the present study, microvascular quantification was undertaken on 25 specimens of mesothelioma and 15 specimens of non-neoplastic mesothelium (NNM), by staining for the antigens CD34 and CD31. Areas of highest intratumoural microvascular density (IMD) were identified and counted either manually (mIMD) or on a computerized image analysis system (CIAS; iIMD). The two IMDs were significantly correlated with each other (r = 0.736; P < 0.001). The average IMD for MM was significantly (P < 0.001) higher than in NNM. Moreover, each unit increment in iIMD for MM, when regarded as a continuous variable, was significantly (P = 0.001) associated with an increased hazard of about 4 per cent. When regarded as a categorical variable, the patients in the highest tertile (> 58 vessels/field) had a significantly (P < 0.01; log-rank test) shorter survival than patients in the lowest tertile (< 45 vessels/field). This association was independent of the age of the patient and of the histological type or grade of the MM. No association was noted with p53 immunoexpression. Although the mean vascular area of blood vessels measured on the CIAS did not correlate with survival, assessment of IMDs can be an important independent prognostic indicator in malignant mesothelioma.

Evaluation and prognostic value of DNA content and of morphometric parameters in malignant mesothelioma using digital image analysis.

Fifty-seven cases of malignant mesothelioma were analyzed for nuclear diameter, DNA content and ploidy-related parameters, using Feulgen stained paraffin sections with a digital imaging analysis system. Thirty cases had a mean nuclear diameter > 7 microns and 31 cases were classified as near-diploid. A statistically significant correlation between survival and the mean nuclear diameter (P = 0.0006) and between survival and DNA index (P = 0.007) was obtained. For other DNA content parameters (proliferation index, 5c exceeding rate), only one of the two statistical tests showed a significant correlation with survival while the other test was of borderline significance. In this malignant mesothelioma population, the prognosis for patients with the epithelial type was better than for those with sarcomatous tumours (P = 0.01). In this population of patients, about half of the malignant mesotheliomas were aneuploid. The mean nuclear diameter, DNA index analysis and proliferation index analysis of the tumour cells on Feulgen stained paraffin sections can be used as independent prognostic parameters.