http://repub.eur.nl/res/aut/157/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/19280/ 2010-02-01T00:00:00Z Aims: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation. Methods and results: One hundred and seventy cases of SCLC, LCNEC and cases diagnosed as neuroendocrine lung carcinoma before LCNEC had been established as a diagnostic category were retrieved from the archives of the assessor's institutes. A representative haematoxylin and eosin section from each case was selected for review. Batches of cases were circulated among nine pathologists with a special interest in pulmonary pathology. Participants were asked to classify the cases histologically according to the 2004 World Health Organization (WHO) criteria. The diagnoses were collected and κ values calculated. Unanimity of diagnosis was achieved for only 20 cases; a majority diagnosis was reached for 115 cases. In 35 cases no consensus diagnosis could be reached. There was striking variability amongst assessors in diagnosing SCLC and LCNEC. The overall level of agreement for all cases included in this study was fair (κ = 0.40). Conclusions: Using non-preselected cases, the morphological WHO criteria for diagnosing SCLC and LCNEC leave room for subjective pathological interpretation, which results in imprecise categorization of SCLC and LCNEC cases. http://repub.eur.nl/res/pub/19343/ 2009-01-20T00:00:00Z Background - Reports on outcome after the Ross procedure are limited by small study size and show variable durability results. A systematic review of evidence on outcome after the Ross procedure may improve insight into outcome and potential determinants. Methods and Results - A systematic review of reports published from January 2000 to January 2008 on outcome after the Ross procedure was undertaken. Thirty-nine articles meeting the inclusion criteria were allocated to 3 categories: (1) consecutive series, (2) adult patient series, and (3) pediatric patient series. With the use of an inverse variance approach, pooled morbidity and mortality rates were obtained. Pooled early mortality for consecutive, adult, and pediatric patients series was 3.0% (95% confidence interval [CI], 1.8 to 4.9), 3.2% (95% CI, 1.5 to 6.6), and 4.2% (95% CI, 1.4 to 11.5). Autograft deterioration rates were 1.15% (95% CI, 1.06 to 2.06), 0.78% (95% CI, 0.43 to 1.40), and 1.38%/patient-year (95% CI, 0.68 to 2.80), respectively, and for right ventricular outflow tract conduit were 0.91% (95% CI, 0.56 to 1.47), 0.55% (95% CI, 0.26 to 1.17), and 1.60%/patient-year (95% CI, 0.84 to 3.05), respectively. For studies with mean patient age >18 years versus mean patient age ≤ 18 years, pooled autograft and right ventricular outflow tract deterioration rates were 1.14% (95% CI, 0.83 to 1.57) versus 1.69% (95% CI, 1.02 to 2.79) and 0.65% (95% CI, 0.41 to 1.02) versus 1.66%/patient-year (95% CI, 0.98 to 2.82), respectively. Conclusions - The Ross procedure provides satisfactory results for both children and young adults. Durability limitations become apparent by the end of the first postoperative decade, in particular in younger patients. http://repub.eur.nl/res/pub/4974/ 1997-01-01T00:00:00Z Background Angioscopy surpasses other diagnostic tools, such as angiography and intravascular ultrasound, in detecting arterial thrombus. This capability arises in part from the unique ability of angioscopy to assess true color during imaging. In practice, hardware-induced chromatic distortions and the subjectivity of human color perception substantially limit the theoretic potential of angioscopic color. We used a novel application of tristimulus colorimetry to quantify thrombus color to both aid in its detection and assess its composition. Methods and Results A series of human thrombus models were constructed in vitro. Spatial homogeneity was ensured by light and electron microscopy. Quantitative colorimetric angioscopic analysis demonstrated excellent measurement reproducibility (mean difference, 0.07% to 0.17%), unaffected by illuminating light intensity (coefficient of variation, 0.21% to 3.67%). Colorimetric parameters C1 and C2 were strongly correlated (r=.99, P<.0001) with thrombus erythrocyte concentration. Principal components analysis transformed these parameters into a single value, the thrombus erythrocyte index, with little (0.06%) loss of content. Measured and predicted concentrations were similar (mean difference, 0.16 erythrocytes per 1 ng). Randomly ordered images were also subjected to visual analysis by three experienced angioscopists, with suboptimal levels of both intraobserver (mean =0.63) and interobserver (mean =0.48) agreement. In addition, visual ranking resulted in a Kendall rank coefficient of 0.72 to 0.76 versus a perfect 1.00 from quantitative measurement. Conclusions Quantitative colorimetric angioscopic analysis provides a new, objective, and reproducible analytic tool for assessing angioscopic images of human thrombus. Even under ideal circumstances, experienced angioscopists do a poor job of assessing color (and therefore composition) of human thrombi. This technique can, for the first time, provide quantitative information of thrombus composition during routine diagnostic imaging. http://repub.eur.nl/res/pub/4600/ 1994-01-01T00:00:00Z OBJECTIVES. The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND. Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of extracellular matrix proteins. The applicability to humans of experimental animal models of these processes has been questioned. METHODS. Primary atherosclerotic and restenotic lesions were excised by percutaneous directional coronary atherectomy in 93 patients. Smooth muscle cells were cultivated by an explant technique and identified by their morphology in culture, ultrastructural features under electron microscopy and immunostaining using monoclonal antibodies to smooth muscle cell alpha-actin. Proliferation in secondary culture was assessed with growth curves and the synthesis of collagen and sulfated glycosaminoglycans by the incorporation of 3H-proline and 35S-sulfate, respectively. These studies were also performed in cells derived from human umbilical artery media. RESULTS. Success rates for primary (45%) and secondary (12%) culture of coronary cells were not influenced by clinical variables or lesion category. Primary culture success was improved by the presence of organized thrombus in the plaque and in relation to increased maximal cell density of the atherectomy specimen. Restenotic cells displayed more rapid growth than did cells of primary atherosclerotic origin, which grew in a manner similar to that of umbilical artery cells. Mean calculated population-doubling times for the three cell groups were 52 h (95% confidence interval [CI] 48 to 58 h), 71 h (95% CI 62 to 83 h) and 74 h (95% CI 65 to 84 h), respectively. Restenotic and primary atherosclerotic cells did not differ in the synthesis of collagen ([mean +/- SEM] 0.034 +/- 0.004 vs. 0.033 +/- 0.004 nmol isotope.microgram protein-1, p = NS) or sulfated glycosaminoglycans (11.47 +/- 1.07 vs. 15.37 +/- 3.10 nmol isotope.microgram protein-1, p = NS), but the coronary cells synthesized significantly more collagen and sulfated glycosaminoglycans than did umbilical artery cells (0.019 +/- 0.004 and 5.43 +/- 1.00 nmol isotope.microgram protein-1, respectively, both p < 0.05). CONCLUSIONS. These data indicate that increased smooth muscle cell proliferation contributes to coronary restenosis in humans and support the concept that the extracellular matrix synthesis of adult smooth muscle cells is important to lesion formation. http://repub.eur.nl/res/pub/4494/ 1993-01-01T00:00:00Z OBJECTIVES. To gain insight into the mechanism of stenting in humans and its short- and long-term implications, we studied the vascular wall of saphenous vein aortocoronary bypass grafts after implantation of the Wallstent. BACKGROUND. The implantation of a stent in aortocoronary bypass grafts may provide an alternative solution for revascularization in patients who are poor candidates for reoperation. Because human histopathologic findings after stenting with the Wallstent have not previously been described in detail, we examined graft segments that were surgically retrieved from 10 patients (21 stents) at 3 days to 10 months after implantation of the stent. METHODS. The grafts were examined by a combination of the following techniques: light microscopy, immunocytochemistry and both scanning and transmission electron microscopy. RESULTS. Early observations revealed that large amounts of platelets and leukocytes adhered to the stent wires during the first few days. At 3 months, the wires were embedded in a layered new intimal thickening, consisting of smooth muscle cells in a collagenous matrix. In addition, foam cells were abundant near the wires. Extracellular lipids and cholesterol crystals were found after 6 months. Smooth muscle cells and extracellular matrix formed the predominant component of restenosis. This new intimal thickening was lined with endothelium, in some cases showing defect intercellular junctions and abnormal adherence of leukocytes and platelets as late as 10 months after implantation. CONCLUSIONS. This type of stent is potentially thrombogenic and seems to be associated with extracellular lipid accumulation in venous aortocoronary bypass grafts. http://repub.eur.nl/res/pub/4509/ 1993-01-01T00:00:00Z -- http://repub.eur.nl/res/pub/4515/ 1993-01-01T00:00:00Z OBJECTIVES. The purpose of this review is to assess the value and limitations of balloon angioplasty for the treatment of saphenous vein bypass graft obstructions. The potential efficacy of new interventional techniques is discussed. BACKGROUND. Treatment of ischemia due to saphenous vein bypass graft obstructions poses a difficult problem that will be encountered more often as the pool of surgically treated patients continues to accumulate. Reoperation is technically demanding and is associated with high mortality and morbidity rates. Balloon angioplasty may provide a suitable alternative. METHODS. The review proposes a classification of patients with attempted saphenous vein graft angioplasty according to expected early and late outcome based on the data obtained from the relevant published data and personal experience. RESULTS. Angioplasty of a nonocclusive obstruction in a saphenous vein bypass graft has an initial success rate of approximately 90% and is a safe procedure (procedural death rate < 1%, myocardial infarction rate < 4%). The overall average restenosis rate is 42%. Surgical standby is limited and technically difficult. Angioplasty of chronic total occlusions in old grafts is associated with poor initial and long-term results. The long-term clinical results are unfavorable because of the continuing progression of disease in nontreated vein graft segments and native coronary arteries, in addition to the high restenosis rate. New techniques, although promising, have shown neither better initial results nor reduction of restenosis. Stent placement may be useful in longer graft lesions containing friable material. CONCLUSIONS. Patients may be classified into three groups according to expected early and late outcome on the basis of 1) unfavorable graft anatomy, 2) risk of cardiogenic shock in event of acute graft closure, and 3) age of grafts. The three groups are 1) those with an initial high success, low procedural risk and low restenosis rate; 2) those with an initial high success but high procedural risk and moderate to high restenosis rate; and 3) those with a low success, high risk and high restenosis rate. Balloon angioplasty to treat lesions in venous bypass grafts should be considered a palliative procedure, not a long-term solution, for ongoing progression of coronary artery and vein graft disease. The induced high restenosis rate remains a significant problem. http://repub.eur.nl/res/pub/4518/ 1993-01-01T00:00:00Z -- http://repub.eur.nl/res/pub/4525/ 1993-01-01T00:00:00Z -- http://repub.eur.nl/res/pub/4538/ 1993-01-01T00:00:00Z BACKGROUND: Coronary atherectomy provides a unique opportunity to obtain plaque tissue from a wide variety of clinical syndromes. We investigated the relation between the clinical status and histopathological substrate of tissue retrieved during directional coronary atherectomy and the proliferative and migratory potential of smooth-muscle cells judged from successful outgrowth during cell culture. METHODS: After directional coronary atherectomy, tissue samples were examined macroscopically, divided into two equal pieces, and separately subjected to cell culture and histopathological study. Cell culture was performed using an explant technique. In-vitro smooth-muscle cell outgrowth was related to clinical and histological variables. RESULTS: Atherosclerotic tissue was obtained from 98 consecutive atherectomy procedures. Histological examination revealed a broad spectrum of appearances, ranging from complex atheroma containing dense fibrous tissue, calcium deposits, macrophages, and necrotic debris to neointimal proliferation and organized thrombi. Smooth-muscle cell outgrowth was observed in 43 of the 98 samples (44%). Although not affected by any of the clinical variables, cell outgrowth was influenced by histological variables, in particular the presence of organizing thrombi. Outgrowth was successful in eight out of 10 samples with thrombus (80%) and in only 35 out of 88 (40%) without (P = 0.03). CONCLUSION: The presence of organizing thrombi in the retrieved tissue facilitates smooth-muscle cell outgrowth and suggests an enhanced proliferative and migratory potential. These findings may be relevant to the understanding of neointimal proliferation in coronary syndromes where mural thrombosis is likely to occur. http://repub.eur.nl/res/pub/4467/ 1992-01-01T00:00:00Z http://repub.eur.nl/res/pub/4488/ 1992-01-01T00:00:00Z Abstract OBJECTIVES: The safety and long-term results of directional coronary atherectomy in stented coronary arteries were determined. In addition, tissue studies were performed to characterize the development of restenosis. METHODS: Directional coronary atherectomy was performed in restenosed stents in nine patients (10 procedures) 82 to 1,179 days after stenting. The tissue was assessed for histologic features of restenosis, smooth muscle cell phenotype, markers of cell proliferation and cell density. A control (no stenting) group consisted of 13 patients treated with directional coronary atherectomy for restenosis 14 to 597 days after coronary angioplasty, directional coronary atherectomy or laser intervention. RESULTS: Directional coronary atherectomy procedures within the stent were technically successful with results similar to those of the initial stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with angiographic follow-up, three had restenosis requiring reintervention (surgery in two and repeat atherectomy followed by laser angioplasty in one). Intimal hyperplasia was identified in 80% of specimens after stenting and in 77% after coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76% of the intimal cells showed morphologic features of a contractile phenotype by electron microscopy 47 to 185 days after coronary intervention. Evidence of ongoing proliferation (proliferating cell nuclear antigen antibody studies) was absent in all specimens studied. Although wide individual variability was present in the maximal cell density of the intimal hyperplasia, there was a trend toward a reduction in cell density over time. CONCLUSIONS: Although atherectomy is feasible for the treatment of restenosis in stented coronary arteries and initial results are excellent, recurrence of restenosis is common. Intimal hyperplasia is a nonspecific response to injury regardless of the device used and accounts for about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic modulation toward a contractile phenotype are early events and largely completed by the time of clinical presentation of restenosis. Restenotic lesions may be predominantly cellular, matrix or a combination at a particular time after a coronary procedure. http://repub.eur.nl/res/pub/4415/ 1991-01-01T00:00:00Z http://repub.eur.nl/res/pub/4421/ 1991-01-01T00:00:00Z OBJECTIVE: To assess by quantitative analysis the immediate angiographic results of directional coronary atherectomy. To compare the effects of successful atherectomy with those of successful balloon dilatation in a series of patients with matched lesions. DESIGN--Case series. SETTING--Tertiary referral centre. PATIENTS--62 patients in whom directional coronary atherectomy was attempted between 7 September 1989 and 31 December 1990. INTERVENTIONS--Directional coronary atherectomy. MAIN OUTCOME MEASURES--Increase in minimal luminal diameter of coronary artery segment. RESULTS--Angiographic success on the basis of intention to treat was obtained in 54 patients (87%). In four patients the lesion could not be crossed by the atherectomy device; all four had an uneventful conventional balloon angioplasty. Four of the 58 patients who underwent atherectomy were subsequently referred for coronary bypass surgery because of failure or complications; three of them sustained a transmural infarction. In the successful cases, coronary atherectomy resulted in an increase in the minimal luminal diameter from 1.1 mm to 2.5 mm with a concomitant decrease of the diameter stenosis from 62% to 22%. In the subset of 37 patients in which the changes induced were compared with conventional balloon angioplasty atherectomy increased the minimal luminal diameter more than balloon angioplasty (1.6 v 0.8 mm; p less than 0.0001). Conventional histology showed media or adventitia in 26% of the atherectomy specimens. In hospital complications occurred in six patients who had undergone a successful procedure: two transmural infarctions, two subendocardial infarctions, one transient ischaemia attack, and one death due to delayed rupture of the atherectomised vessel. All patients were clinically evaluated at one and six months. One patient had persisting angina (New York Heart Association class II), one patient sustained a myocardial infarction, one patient underwent a percutaneous transluminal coronary angioplasty for early restenosis, and one patient underwent coronary bypass surgery because of a coronary aneurysm formation. At six months 80% (36/47) of the patients were symptom free. CONCLUSIONS--Coronary atherectomy achieved a better immediate angiographic result than balloon angioplasty; however, in view of the complication rate in this preliminary series, which may be related to a learning curve, a randomised study is needed to show whether this procedure is as safe as a conventional balloon angioplasty.