Fractal Characteristics of May-Grünwald-Giemsa Stained Chromatin Are Independent Prognostic Factors for Survival in Multiple Myeloma

The use of computerized image analysis for the study of nuclear texture features has provided important prognostic information for several neoplasias. Recently fractal characteristics of the chromatin structure in routinely stained smears have shown to be independent prognostic factors in acute leukemia. In the present study we investigated the influence of the fractal dimension (FD) of chromatin on survival of patients with multiple myeloma.We analyzed 67 newly diagnosed patients from our Institution treated in the Brazilian Multiple Myeloma Study Group. Diagnostic work-up consisted of peripheral blood counts, bone marrow cytology, bone radiograms, serum biochemistry and cytogenetics. The International Staging System (ISS) was used. In every patient, at least 40 digital nuclear images from diagnostic May-Grünwald-Giemsa stained bone marrow smears were acquired and transformed into pseudo-3D images. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R(2) values in the log-log plots. The influence of diagnostic features on overall survival was analyzed in Cox regressions. Patients that underwent autologous bone marrow transplantation were censored at the day of transplantation.Median age was 56 years. According to ISS, 14% of the patients were stage I, 39% were stage II and 47% were stage III. Additional features of a bad prognosis were observed in 46% of the cases. When stratifying for ISS, both FD and its goodness-of-fit were significant prognostic factors in univariate analyses. Patients with higher FD values or lower goodness-of-fit showed a worse outcome. In the multivariate Cox-regression, FD, R(2), and ISS stage entered the final model, which showed to be stable in a bootstrap resampling study.Fractal characteristics of the chromatin texture in routine cytological preparations revealed relevant prognostic information in patients with multiple myeloma

Segmented nucleus (left) of a myeloma cell and its pseudo 3D transformation (middle).

<p>On the right side, the log-log-plot for the determination of the fractal dimension (FD), which is calculated from the slope of the ideal regression line (black) obtained by curve fitting. X-axis shows the logarithms of the inverse values of the size of the structuring element and y axis the logarithmic values of the fractal areas. (compare with the main text). R² represents the goodness-of-fit of the real values (red), when compared with ideal regression line (black) and can be interpreted as a measure of “fractal quality”.</p

Segmented images of myeloma cell nuclei, classified by their grade of maturity and chromatin structure.

<p>A: Nucleus with a more mature chromatin structure; its FD was 2.074935 and R² = 0.999330. B: a more immature nucleus with a less organized chromatin structure presenting FD = 2.223 and R² = 0.99896. C: Nucleus with a blastic feature: FD = 2.1759 and R² = 0.9961. D: Nucleus with irregular and disorganized chromatin: FD = 2.2629 and R² = 0.99931</p

Clinical variables of the patients.

<p>Clinical variables of the patients.</p

Mean fractal dimension as a function of the number of nuclei examined in an individual case.

<p>The mean value stabilized after examination of 30–40 cells.</p

Overall survival of the myeloma patients categorized by ISS stage.

<p>Kaplan-Meier plot. Log rank-test: p = 0.0005.</p

Overall survival categorized by the presence or absence of additional risk factors [2].

<p>Kaplan-Meier plot. Log rank-test: p = 0.02.</p

Evolution of collectivity along the N=Z line: The 84Mo nucleus

The reaction 58Ni(28Si,2nγ) at 90 MeV incident energy has been used to populate the N=Z nucleus 84Mo. The GASP array was used together with the ISIS Silicon ball, which allowed a subtraction of the charged particle channels in the γ-γ coincidences. The only known transition 21+→01+ of 443.8 keV in 84Mo has been found in coincidence with a γ ray of 673.5±0.4 keV which was assigned as the second (41+→21+) yrast transition. The behavior of the resulting yrast line indicates that 84Mo is a transitional nucleus. The correlation between the excitation energies of the 21+ and 41+ levels of the N=Z nuclei reveals a systematic deviation from the average behavior defined by all collective even-even nuclei

Epidemiology, clinical features and diagnostic work-up of cystic neoplasms of the pancreas: Interim analysis of the prospective PANCY survey

Introduction: A prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines. Methods: An online data sheet was built. Results: Fifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up. Conclusions: This prospective study offers a reliable real-life picture of the diagnostic work-up CPN