Effects of hematopoietic growth factors on purified bone marrow progenitor cells

We have used highly enriched hematopoietic progenitor cells and in-vitro culture to examine the following questions: 1. The effects of recombinant lL-3 and GM-CSF on proliferation and differentiation of enriched hematopoietic progenitor cells have not been clearly defined: - how do IL~3 and GM~CSF compare with respect to number and types of colonies induced? -to what extent do accessory cells influence colony formation induced by IL-3 and GM~CSF? {chapters 2 and 3) 2. The effects of recombinant G-CSF, M~CSF and IL-6 on enriched hematopoietic progenitor cells in connection with IL-3 and GM~CSF have not been fully elucidated: ~ what is the role of synergistic effects between G~CSF, M-CSF and IL~6 on the one hand and IL~3 and GM~CSF on the other hand, on the proliferation and differentiation of colony forming cells? (chapters 4, 5 and 6) 3. Consistent results on the effects of ll-1 on proliferation of immature bone marrow cells are lacking: ~does ll-1 directly induce proliferation? -what is the role of GM~CSF and TNF as mediators of the IL-1 effect? (chapter 7) 2

Prognostic factors in renal-cell carcinoma: Immunohistochemical detection of p53 protein versus clinico-pathological parameters

Immunoreactivity forp53 protein was assessed in 100 cases of primary renal-cell carcinoma (RCC). The results were correlated with clinical survival data (follow-up 24 to 84 months: mean: 39 months) and with clinico-pathological parameters, including nuclear grade, tumour stage, cell type, tumour architecture and tumour diameter. In all, 32% of the tumours were p53-positive; there was no difference in survival between p53-positive and -negative cases. Similarly, p53 expression did not correlate with any of the clinico-pathological parameters mentioned. Nuclear grade (grade 1 + 2 vs. grade 3 + 4) had a striking impact on prognosis and so, to a lesser extent, did tumour stage and the occurrence of a spindle-cell component. The immunohistochemical detection of p53 in RCC is not of prognostic value. The estimation of nuclear grade, however is a major predictor of prognosis

Dissecting the gray zone between follicular lymphoma and marginal zone lymphoma using morphological and genetic features

Nodal marginal zone lymphoma is a poorly defined entity in the World Health Organization classification, based largely on criteria of exclusion and the diagnosis often remains subjective. Follicular lymphoma lacking t(14;18) has similar characteristics which results in a major potential diagnostic overlap which this study aims to dissect. Four subgroups of lymphoma samples (n=56) were analyzed with high-resolution array comparative genome hybridization: nodal marginal zone lymphoma, t(14;18)-negative follicular lymphoma, localized t(14:18)-positive follicular lymphoma and disseminated t(14;18)-positive follicular lymphoma. Gains on chromosomes 7, 8 and 12 were observed in all subgroups. The mean number of aberrations was higher in disseminated t(14;18)-positive follicular lymphoma than in localized t(14:18)-positive follicular lymphoma (P<0.01) and the majority of alterations in localized t(14:18)-positive follicular lymphoma were also found in disseminated t(14;18)-positive follicular lymphoma. Nodal marginal zone lymphoma was marked by 3q gains with amplifications of four genes. A different overall pattern of aberrations was seen in t(14;18)-negative follicular lymphoma compared to t(14;18)-positive follicular lymphoma. t(14;18)-negative follicular lymphoma is characterized by specific (focal) gains on chromosome 3, as observed in nodal marginal zone lymphoma. Our results support the notion that localized t(14:18)-positive follicular lymphoma represents an early phase of disseminated t(14;18)-positive follicular lymphoma. t(14;18)-negative follicular lymphoma bears aberrations that are more like those in nodal marginal zone lymphoma, suggesting a relation between these groups

Reproducibility of histologic classification in nonfibrotic myeloproliferative neoplasia

Item does not contain fulltextEarly phases of polycythemia vera, essential thrombocythemia, and primary myelofibrosis (PMF) can be difficult to distinguish by morphologic studies alone because they share many morphologic characteristics. Histologic criteria according to the 2008 World Health Organization (WHO) classification are part of the myeloproliferative neoplasia (MPN) diagnosis. Our aim was to assess the reproducibility of morphologic characteristics and determine their relative importance for histologic diagnoses on selected trephine biopsy sections. For the study, 56 prefibrotic MPN trephine specimens were blindly reviewed by 4 hematopathologists using a scoring list of 16 histologic characteristics mentioned in the WHO classification. Consensus was defined as agreement by 3 of 4 hematopathologists. High degrees of consensus were reached for individual major morphologic features used in the WHO classification, especially for the nuclear features of megakaryocytes (83%). Some of the features correlated positively or negatively with the histologic diagnosis of PMF. Consensus for the histologic classification of MPN was reached in 39 (70%) of 56 cases without knowledge of clinical data. This finding indicates a difference in the relative importance assigned to individual histologic characteristics by different hematopathologists

Interobserver variability of laryngeal mucosal premalignant lesions: a histopathological evaluation.

Item does not contain fulltextThe objective of this study is to measure interobserver variability in the classification of laryngeal mucosal premalignant lesions by reassessing the histopathology of previously diagnosed cases and to determine the possible therapeutic consequences of disagreement among observers. Histopathological assessment of 110 laryngeal mucosal premalignant lesions was done by three pathologists. Each slide had to be classified according to the World Health Organization, Squamous Intraepithelial Neoplasia, and the Ljubljana Squamous Intraepithelial Lesions systems. After the independent assessment, a joint meeting took place. To assess the relation between histopathological grading and subsequent clinical management, we created a two- and a three-grade system besides one comprising all options. For all analyses, the SAS/STAT statistical software was used. The highest unweighted kappa-values concerning the all-options system are observed for the Squamous Intraepithelial Neoplasia classification (0.28, 95% confidence interval 0.23-0.33), followed by the World Health Organization and Ljubljana classifications. For the two-grade system the Ljubljana classification shows the highest unweighted kappa-values (0.50, 95%, 0.39-0.61), followed by the World Health Organization and Squamous Intraepithelial Neoplasia classifications. For the three-grade system, the unweighted kappa-values are similar. The implementation of weighted kappa-values led to higher scores within all three classification systems, although these did not exceed 0.55 (moderate agreement). Given the high level of consensus, simultaneous pathological assessment may be said to provide added value in comparison with independent assessment. In the current study, no clear tendency is observed in favor of any one classification system. The proposed three-grade system could be an improved histopathological tool because it is easier to correlate with clinical decision making and because it yields better unweighted kappa-values and proportions of concordance than the all-options system. Furthermore, clinical management could benefit from assessment by more than one pathologist in suspected cases of dysplasia or carcinoma.1 juli 201

Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug‐Eluting Stent Implantation: Per‐Protocol Analysis of the GLOBAL LEADERS Trial

International audienceBackground In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P =0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435