Two-Step Strategy for Optimizing the Preoperative Classification of Adnexal Masses in a University Hospital, Using International Ovarian Tumor Analysis Models: Simple Rules and Assessment of Different NEoplasias in the adneXa Model.

OBJECTIVES: To evaluate the performance of a two-step strategy compared with the International Ovarian Tumor Analysis (IOTA) - Assessment of Different NEoplasias in the adneXa (ADNEX) model for preoperative classification of adnexal masses. METHODS: An ambispective diagnostic accuracy study based on ultrasound data collected at one university hospital between 2012 and 2018. Two ultrasonographers classified the adnexal masses using IOTA Simple Rules (first step). Not classifiable masses were evaluated using the IOTA ADNEX model (second step). Also, all masses were classified using the IOTA ADNEX model. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-), and receiver operating characteristic (ROC) curve were estimated. A P value of <.05 was used to determine statistical significance. RESULTS: The study included 548 patients and 606 masses. Patients' median age was 41 years with an interquartile range between 32 and 51 years. In the first step, 89 (14%) masses were not classifiable. In the second step, 55 (61.8%) masses were classified as malignant. Furthermore, for the totality of 606 masses, the IOTA ADNEX model estimated the probability that 126 (20.8%) masses were malignant. The two-step strategy had a sensitivity, specificity, PPV, NPV, LR+, LR-, and ROC curve of 86.8%, 91.01%, 51.9%, 98.4%, 9.7, 0.1, and 0.889, respectively; compared to IOTA ADNEX model that had values of 91.8%, 87.16%, 44.4%, 99%, 7.1, 0.09, and 0.895, respectively. CONCLUSION: The two-step strategy shows a similar diagnostic performance when compared to the IOTA ADNEX model. The IOTA ADNEX model involves only one step and can be more practical, and thus would be recommended to use.

Next-generation sequencing and FISH studies reveal the appearance of gene mutations and chromosomal abnormalities in hematopoietic progenitors in chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a highly genetically heterogeneous disease. Although CLL has been traditionally considered as a mature B cell leukemia, few independent studies have shown that the genetic alterations may appear in CD34+ hematopoietic progenitors. However, the presence of both chromosomal aberrations and gene mutations in CD34+ cells from the same patients has not been explored. METHODS: Amplicon-based deep next-generation sequencing (NGS) studies were carried out in magnetically activated-cell-sorting separated CD19+ mature B lymphocytes and CD34+ hematopoietic progenitors (n = 56) to study the mutational status of TP53, NOTCH1, SF3B1, FBXW7, MYD88, and XPO1 genes. In addition, ultra-deep NGS was performed in a subset of seven patients to determine the presence of mutations in flow-sorted CD34+CD19- early hematopoietic progenitors. Fluorescence in situ hybridization (FISH) studies were performed in the CD34+ cells from nine patients of the cohort to examine the presence of cytogenetic abnormalities. RESULTS: NGS studies revealed a total of 28 mutations in 24 CLL patients. Interestingly, 15 of them also showed the same mutations in their corresponding whole population of CD34+ progenitors. The majority of NOTCH1 (7/9) and XPO1 (4/4) mutations presented a similar mutational burden in both cell fractions; by contrast, mutations of TP53 (2/2), FBXW7 (2/2), and SF3B1 (3/4) showed lower mutational allele frequencies, or even none, in the CD34+ cells compared with the CD19+ population. Ultra-deep NGS confirmed the presence of FBXW7, MYD88, NOTCH1, and XPO1 mutations in the subpopulation of CD34+CD19- early hematopoietic progenitors (6/7). Furthermore, FISH studies showed the presence of 11q and 13q deletions (2/2 and 3/5, respectively) in CD34+ progenitors but the absence of IGH cytogenetic alterations (0/2) in the CD34+ cells. Combining all the results from NGS and FISH, a model of the appearance and expansion of genetic alterations in CLL was derived, suggesting that most of the genetic events appear on the hematopoietic progenitors, although these mutations could induce the beginning of tumoral cell expansion at different stage of B cell differentiation. CONCLUSIONS: Our study showed the presence of both gene mutations and chromosomal abnormalities in early hematopoietic progenitor cells from CLL patients.

MiRNA expression profile of chronic lymphocytic leukemia patients with 13q deletion.

Deletion 13q (13q-) is the most common cytogenetic aberration in chronic lymphocytic leukemia (CLL) and is associated with the most favorable prognosis as the sole cytogenetic abnormality. However, it is heterogeneous whereby CLL patients with higher percentages of 13q- cells (13q-H) have a more aggressive clinical course and a distinct gene expression profile. The microRNA (miRNA) expression profile of CLL gives additional biological and prognostic information, but its expression in 13q- CLL has not been examined in detail. The miRNA expression of clonal B cell lymphocytes (CD19+ cells) of 38 CLL patients and normal B cells of six healthy donors was analyzed. CLL patients with higher percentages of 13q- cells (≥80%) showed a different level of miRNA expression from patients with lower percentages (<80%). Interestingly, miR-143 was downregulated and miR-155 was overexpressed in 13q-H. This deregulation affected important validated target genes involved in apoptosis (BCL2, MDM2, TP53INP1) and proliferation (KRAS, PI3K-AKT signaling), that could lead to decreased apoptosis and increased proliferation in 13q-H patients. This study provides new evidence about the heterogeneity of the 13q deletion in CLL patients, showing that miRNA regulation could be involved in several significant pathways deregulated in CLL patients with a high number of losses in 13q.

Informal Caregivers of Palliative Oncohematologic Patients: The Invisible Guests: An Exhaustive Review of the Literature Available.

Informal caregivers are crucial members of the teams that care for palliative patients with cancer, including those with oncohematological malignancies. Publications concerning specific aspects of this latter group of carers are limited. This literature review indicates that palliative oncohematologic patients' caregivers do not differ from those of patients with solid tumors in ethical and related problems. However, there are specific problems for the former group with regard to negotiating the curative system, which are experienced as distressing, often without support from the health system and without offers of the possibility of being referred to palliative teams that they would have valued as very positive. Although this tendency seems to be changing, there is still considerable work to be done to improve the role of these carers.

Human maternal heritage in Andalusia (Spain): its composition reveals high internal complexity and distinctive influences of mtDNA haplogroups U6 and L in the western and eastern side of region.

BACKGROUND: The archeology and history of the ancient Mediterranean have shown that this sea has been a permeable obstacle to human migration. Multiple cultural exchanges around the Mediterranean have taken place with presumably population admixtures. A gravitational territory of those migrations has been the Iberian Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by means of control region sequencing and PCR-RFLP typing, of autochthonous Andalusians originating from the coastal provinces of Huelva and Granada, located respectively in the west and the east of the region. RESULTS: The mtDNA haplogroup composition of these two southern Spanish populations has revealed a wide spectrum of haplogroups from different geographical origins. The registered frequencies of Eurasian markers, together with the high incidence and diversification of African maternal lineages (15% of the total mitochondrial variability) among Huelva Andalusians when compared to its eastwards relatives of Granada and other Iberian populations, constitute relevant findings unknown up-to-date on the characteristics of mtDNA within Andalusia that testifies a female population substructure. Therefore, Andalusia must not be considered a single, unique population. CONCLUSIONS: The maternal legacy among Andalusians reflects distinctive local histories, pointing out the role of the westernmost territory of Peninsular Spain as a noticeable recipient of multiple and diverse human migrations. The obtained results underline the necessity of further research on genetic relationships in both sides of the western Mediterranean, using carefully collected samples from autochthonous individuals. Many studies have focused on recent North African gene flow towards Iberia, yet scientific attention should be now directed to thoroughly study the introduction of European genes in northwest Africa across the sea, in order to determine its magnitude, timescale and methods, and to compare them to those terrestrial movements from eastern Africa and southwestern Asia.

Transfusion in palliative cancer patients: a review of the literature.

BACKGROUND: Transfusion is not an exceptional circumstance in palliative cancer patients (PCPs). This makes it necessary to confront not only medical aspects but also those of infrastructure and ethical issues. On some occasions, literature needs to be consulted to work out the best approach in a patient's particular case. Our aim was to review the literature contained in PubMed and EMBASE so as to find out about the information available on transfusion in PCPs. METHODS: A search for literature was carried out in databases PubMed and EMBASE, using "transfusion," "cancer," "end-of-life care," "terminal care," and "palliative care" as key words. Publications were classified according to the main topic discussed (clinical, infrastructure, and ethics) and the information included in each article critically assessed. RESULTS: We found 334 articles but only 43 were considered valuable for the present study. Of these 43 articles, 21 deal with clinical topics while 12 deal with infrastructure and 10 with ethical issues. There is an absolute lack of randomized controlled trials or clinical guidelines. Trigger parameters for transfusion are not clearly established. Benefits of the procedure are shortly experienced and remain controversial. Home transfusions are encouraged, but this sole procedure has not been demonstrated to be cost effective. Different cultures, cases, and realities illustrate the diversity of the ethical management of transfusion in PCPs. DISCUSSION: Although transfusion is certainly a common practice in PCPs, there is a relative lack of literature on this topic. Publications are unconnected and hardly any prospective studies have been performed. A large part of the little literature available only concerns descriptive and very general aspects of the issue. As transfusional products and financial and human resources are finite, it would be desirable to establish clear research lines on the different aspects considered (clinical, infrastructure, and ethical) that can help clinicians, nurses, patients, and carers to make a decision.

Prognostic impact of the number of methylated genes in myelodysplastic syndromes and acute myeloid leukemias treated with azacytidine.

The prognostic impact of the aberrant hypermethylation in response to azacytidine (AZA) remains to be determined. Therefore, we have analyzed the influence of the methylation status prior to AZA treatment on the overall survival and clinical response of myeloid malignancies. DNA methylation status of 24 tumor suppressor genes was analyzed by methylation-specific multiplex ligation-dependent probe amplification in 63 patients with myelodysplastic syndromes and acute myeloid leukemia treated with azacytidine. Most patients (73 %) showed methylation of at least one gene, but only 12 % of patients displayed ≥3 methylated genes. The multivariate analysis demonstrated that the presence of a high number (≥2) of methylated genes (P = 0.022), a high WBC count (P = 0.033), or anemia (P = 0.029) were independent prognostic factors associated with shorter overall survival. The aberrant methylation status did not correlate with the response to AZA, although four of the five patients with ≥3 methylated genes did not respond. By contrast, favorable cytogenetics independently influenced the clinical response to AZA as 64.7 % of patients with good-risk cytogenetic abnormalities responded (P = 0.03). Aberrant methylation status influences the survival of patients treated with AZA, being shorter in those patients with a high number of methylated genes.

Y-STR genetic diversity in autochthonous Andalusians from Huelva and Granada provinces (Spain).

Seventeen Y-chromosomal short tandem repeats (STRs) were analyzed in 347 healthy, unrelated, autochthonous males from the Andalusian provinces of Huelva (N=167) and Granada (N=180). AmpFlSTR Y-filer PCR Amplification kit (Applied Biosystems) was used to type the Y-STR markers. A total of 156 and 166 different haplotypes for the 17 Y-STR set were detected in Huelva, and Granada, respectively. The same haplotype diversity was found for both samples (0.998±0.001), and the overall discrimination capacity was 0.904. The most common minimal haplotype (DYS19, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393) in both subpopulations was 14-13-16-24-11-13-13, which is also the most frequent haplotype among Atlantic European populations. Comparison analysis using pairwise R(ST) values and Analysis of Molecular Variance (AMOVA) revealed a significant genetic distance between our Andalusian samples and other ones from the northern Iberian fringe (including Basque and Pyrenean populations). However, results from the multi-dimensional scaling analysis (MDS) yielded a well-defined group of Iberian populations separated from the other Mediterranean clusters observed.

Manejo de las complicaciones hemorrágicas en cuidados paliativos oncológicos / Medical management of hemorrhagic complications in oncologic palliative care

Las neoplasias son ampliamente reconocidas como entidades capaces de alterar el equilibrio hemostático del organismo predisponiendo fundamentalmente a la trombosis, aunque también pueden generarse fenómenos hemorrágicos. Este hecho obliga a los equipos de cuidados paliativos a realizar en ocasiones el diagnóstico y tratamiento de estas últimas eventualidades. El presente trabajo realiza primeramente una revisión de la fisiopatología de los fenómenos hemorrágicos en relación con los procesos tumorales y, posteriormente, de las medidas médicas disponibles destinadas al tratamiento de dichos fenómenos y que incluyen: antifibrinoliticos, transfusión de plaquetas, vitamina K, transfusión de plasma fresco congelado, factores específicos, concentrado de factores del complejo protrombínico o factor VII recombinante activado, con especial énfasis en sus indicaciones, complicaciones, problemas en el manejo y aspectos prácticos en este tipo de pacientes.