Fractal characteristics of chromatin, revealed by light or electron microscopy, have been reported during the last 20 years. Fractal features can easily be estimated in digitalized microscopic images ...and are helpful for diagnosis and prognosis of neoplasias. During carcinogenesis and tumor progression, an increase of the fractal dimension (FD) of stained nuclei has been shown in intraepithelial lesions of the uterine cervix and the anus, oral squamous cell carcinomas or adenocarcinomas of the pancreas. Furthermore, an increased FD of chromatin is an unfavorable prognostic factor in squamous cell carcinomas of the oral cavity and the larynx, melanomas and multiple myelomas. High goodness-of-fit of the regression line of the FD is a favorable prognostic factor in acute leukemias and multiple myelomas. The nucleus has fractal and power-law organization in several different levels, which might in part be interrelated. Some possible relations between modifications of the chromatin organization during carcinogenesis and tumor progression and an increase of the FD of stained chromatin are suggested. Furthermore, increased complexity of the chromatin structure, loss of heterochromatin and a less-perfect self-organization of the nucleus in aggressive neoplasias are discussed.
Here we present a study on the use of non-additive entropy to improve the performance of convolutional neural networks for texture description. More precisely, we introduce the use of a local ...transform that associates each pixel with a measure of local entropy and use such alternative representation as the input to a pretrained convolutional network that performs feature extraction. We compare the performance of our approach in texture recognition over well-established benchmark databases and on a practical task of identifying Brazilian plant species based on the scanned image of the leaf surface. In both cases, our method achieved interesting performance, outperforming several methods from the state-of-the-art in texture analysis. Among the interesting results we have an accuracy of 84.4% in the classification of KTH-TIPS-2b database and 77.7% in FMD. In the identification of plant species we also achieve a promising accuracy of 88.5%. Considering the challenges posed by these tasks and results of other approaches in the literature, our method managed to demonstrate the potential of computing deep learning features over an entropy representation.
Prognostic factors in malignant melanoma are currently based on clinical data and morphologic examination. Other prognostic features, however, which are not yet used in daily practice, might add ...important information and thus improve prognosis, treatment, and survival. Therefore a search for new markers is desirable. Previous studies have demonstrated that fractal characteristics of nuclear chromatin are of prognostic importance in neoplasias. We have therefore investigated whether the fractal dimension of nuclear chromatin measured in routine histological preparations of malignant melanomas could be a prognostic factor for survival.
We examined 71 primary superficial spreading cutaneous melanoma specimens (thickness > or = 1 mm) from patients with a minimum follow up of 5 years. Nuclear area, form factor and fractal dimension of chromatin texture were obtained from digitalized images of hematoxylin-eosin stained tissue micro array sections. Clark's level, tumor thickness and mitotic rate were also determined.
The median follow-up was 104 months. Tumor thickness, Clark's level, mitotic rate, nuclear area and fractal dimension were significant risk factors in univariate Cox regressions. In the multivariate Cox regression, stratified for the presence or absence of metastases at diagnosis, only the Clark level and fractal dimension of the nuclear chromatin were included as independent prognostic factors in the final regression model.
In general, a more aggressive behaviour is usually found in genetically unstable neoplasias with a higher number of genetic or epigenetic changes, which on the other hand, provoke a more complex chromatin rearrangement. The increased nuclear fractal dimension found in the more aggressive melanomas is the mathematical equivalent of a higher complexity of the chromatin architecture. So, there is strong evidence that the fractal dimension of the nuclear chromatin texture is a new and promising variable in prognostic models of malignant melanomas.
Treatment-free remission (TFR) is successful in half of the patients with chronic myeloid leukemia who discontinue Imatinib (IM) after sustained molecular response.
In a prospective trial, we used ...pioglitazone for 3 months before stopping IM in 30 patients. Percentages of peripheral blood lymphocyte subsets were assessed before and after treatment. The relation of these data with duration of IM treatment and TRF were examined.
The median time of IM treatment was 117.6 months. After discontinuation, 11 patients had molecular recurrence after 5.2 months (2.4 – 30). The observation time for those remaining in TFR was 46 (26 – 56) months. The independent factors for the maintenance of TFR were the duration of IM treatment and the percentage of double-positive T cells at IM stop.
A longer treatment with imatinib was associated with a longer TFR after discontinuation. Pioglitazone could act as an immunomodulator, increasing DP T cells which may contribute to prevent relapse.
myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic clonal disorders. So, prognostic variables are important to separate patients with a similar biology and clinical outcome. ...We compared the importance of risk stratification in primary MDS of IPSS and WPSS with the just described revision of IPSS (IPSS-R), and examined if variables obtained by bone marrow immunophenotyping could add prognostic information to any of the scores.
In this prospective study of 101 cases of primary MDS we compared the relation of patients' overall survival with WHO types, IPSS, IPSS-R, WPSS and phenotypic abnormalities of hematopoietic precursors. We examined aberrancies in myelomonocytic precursors and CD34(+) cells. Patients were censored when receiving chemotherapy or BM transplantation. Survival analysis was made by Cox regressions and stability of the models was examined by bootstrap resampling.
MEDIAN AGE: 64 years (15-93). WHO types: 2 cases of 5q- syndrome, 7 of RA, 64 of RCDM and 28 of RAEB. In the univariate Cox analysis, increasing risk category of all scores, degree of anemia, higher percentage of BM blasts, higher number of CD34(+) cells and their myeloid fractions besides increasing number of phenotypic abnormalities detected were significantly associated with a shorter survival. In the multivariate analysis comparing the three scores, IPSS-R was the only independent risk factor. Comparing WPSS with phenotypic variables (CD34(+)/CD13(+) cells, CD34(+)/CD13(-) cells and "total alterations") the score and "CD34(+)/CD13(+) cells" remained in the model. When IPSS was tested together with these phenotypic variables, only "CD34(+)/CD13(+) cells", and "total alterations" remained in the model. Testing IPSS-R with the phenotypic variables studied, only the score and "CD34(+)/CD13(+) cells" entered the model.
Immunophenotypic analysis of myelomonocytic progenitors provides additional prognostic information to all clinical scores studied. IPSS-R improved risk stratification in MDS compared to the former scores.
Background The diagnosis of idiopathic atrophoderma of Pasini and Pierini (IAPP) relies on typical clinical features, particularly distinctive pigmented ovular/round depressed plaques. Histologic ...examination often reveals no obvious changes, but patterns of collagen distribution, using multiphoton imaging and second harmonic generation can help track hidden details of tissue organization contributing to atrophy. Objective To identify histologic features that distinguish IAPP from unaffected skin. Methods Eleven patients were included for conventional analyses. Masson trichrome– and Unna-Tanzer orcein–stained sections were evaluated using automated morphometry. Hematoxylin-eosin–stained sections were analyzed by multiphoton imaging using 2-photon excited fluorescence and second harmonic generation. Results No abnormalities were found under light microscopy or by automated quantification. Multiphoton imaging revealed no difference in optical density of either collagen or elastic fibers in lesioned and unaffected skin; however, horizontal collagen fiber organization in lesion specimens increased toward the lower dermis, whereas elastic fibers featured greater disorganization within the upper dermis. Limitations The low number of patients evaluated. Conclusion The atrophic appearance of IAPP lesions reflects changes in organization, but not in collagen and elastic tissue content. Minute organizational differences that are imperceptible to the experienced pathologist and undetectable by automated analyses were revealed by multiphoton analyses, particularly second harmonic generation, in association with texture analyses.
(1) Background: Acute promyelocytic leukemia is curable, but bleeding complications still provoke a high early mortality. Therefore, a fast diagnosis is needed for timely starting treatment. We ...developed a diagnostic algorithm using flow cytometric features for discrimination between acute promyelocytic leukemia (APL) and other types of acute myeloid leukemias (AML). (2) Methods: we analyzed newly diagnosed AMLs where immunophenotyping was performed at diagnosis by an 8-color protocol. The mean fluorescence intensity (MFI) of each antigen used was assessed, and those best separating APL from other types of AML were obtained by a discriminant analysis. Phenotypic characteristics of myeloblasts of normal bone marrow were used as controls. (3) Results: 24 cases of APL and 56 cases of other primary AMLs entered the study. Among non-APL AMLs, 4 had fms-related tyrosine kinase 3 gene internal tandem duplications (FLT3-ITD) mutation, 2 had nucleophosmin (NPM1) and 10 had both mutations. SSC (p < 0.0001), HLA-DR (p < 0.0001), CD13 (p = 0.001), CD64 (p = 0.004) and CD33 (p = 0.002) were differentially expressed, but this was not the case for CD34 (50% of non-APLs had a low expression). In the discriminant analysis, the best differentiation was achieved with SSC and HLA-DR discriminating 91.25% of the patients. (4) Conclusion: MFC could differentiate APL from non-APL AML in the majority of the cases.
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