Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping

Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders (B-CLPD) is becoming increasingly complex due to usage of progressively larger panels of reagents and a high number of World Health Organization (WHO) entities. Typically, data analysis is performed separately for each stained aliquot of a sample; subsequently, an expert interprets the overall immunophenotypic profile (IP) of neoplastic B-cells and assigns it to specific diagnostic categories. We constructed a principal component analysis (PCA)-based tool to guide immunophenotypic classification of B-CLPD. Three reference groups of immunophenotypic data files—B-cell chronic lymphocytic leukemias (B-CLL; n=10), mantle cell (MCL; n=10) and follicular lymphomas (FL; n=10)—were built. Subsequently, each of the 175 cases studied was evaluated and assigned to either one of the three reference groups or to none of them (other B-CLPD). Most cases (89%) were correctly assigned to their corresponding WHO diagnostic group with overall positive and negative predictive values of 89 and 96%, respectively. The efficiency of the PCA-based approach was particularly high among typical B-CLL, MCL and FL vs other B-CLPD cases. In summary, PCA-guided immunophenotypic classification of B-CLPD is a promising tool for standardized interpretation of tumor IP, their classification into well-defined entities and comprehensive evaluation of antibody panels

Inside and out: the activities of senescence in cancer.

The core aspect of the senescent phenotype is a stable state of cell cycle arrest. However, this is a disguise that conceals a highly active metabolic cell state with diverse functionality. Both the cell-autonomous and the non-cell-autonomous activities of senescent cells create spatiotemporally dynamic and context-dependent tissue reactions. For example, the senescence-associated secretory phenotype (SASP) provokes not only tumour-suppressive but also tumour-promoting responses. Senescence is now increasingly considered to be an integrated and widespread component that is potentially important for tumour development, tumour suppression and the response to therapy.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nrc377

A Probabilistic Approach for the Evaluation of Minimal Residual Disease by Multiparameter Flow Cytometry in Leukemic B-Cell Chronic Lymphoproliferative Disorders

Multiparameter flow cytometry has become an essential too] for monitoring response to therapy in hematological malignancies, including B-cell chronic lymphoproliferative disorders (B-CLPD). However, depending on the expertise of the operator minimal residual disease (MRD) can be misidentified, given that data analysis is based on the definition of expert-based bidimensional plots, where an operator selects the subpopulations of interest. Here, we propose and evaluate a probabilistic approach based on pattern classification tools and the Bayes theorem, for automated analysis of flow cytometry data from a group of 50 B-CLPD versus normal peripheral blood B-cells under MRD conditions, with the aim of reducing operator-associated subjectivity. The proposed approach provided a tool for MRD detection in B-CLPD by flow cytometry with a sensitivity of <= 8 x 10(-5) (median of <= 2 x 10(-7)). Furthermore, in 86% of BCLPD cases tested, no events corresponding to normal B-cells were wrongly identified as belonging to the neoplastic B-cell population at a level of <= 10(-7). Thus, this approach based on the search for minimal numbers of neoplastic B-cells similar to those detected at diagnosis could potentially be applied with both a high sensitivity and specificity to investigate for the presence of MRD in virtually all B-CLPD. Further studies evaluating its efficiency in larger series of patients, where reactive conditions and non-neoplastic disorders are also included, are required to confirm these results. (C) 2008 International Society for Advancement of Cytometr

European Society of ColoProctology: guideline for haemorrhoidal disease

Aim: The goal of this European Society of ColoProctology project was to establish a multidisciplinary, international guideline for haemorrhoidal disease (HD) and to provide guidance on the most effective (surgical) treatment for patients with HD. Methods: The development process consisted of six phases. In phase one we defined the scope of the guideline. The patient population included patients with all stages of haemorrhoids. The target group for the guideline was all practitioners treating patients with haemorrhoids and, in addition, healthcare workers and patients who desired information regarding the treatment management of HD. The guideline needed to address both the diagnosis of and the therapeutic modalities for HD. Phase two consisted of the compilation of the guideline development group (GDG). All clinical members needed to have affinity with the diagnosis and treatment of haemorrhoids. Further, attention was paid to the geographical distribution of the clinicians. Each GDG member identified at least one patient in their country who could read English to comment on the draft guideline. In phase three review questions were formulated, using a reversed process, starting with possible recommendations based on the GDG’s knowledge. In phase four a literature search was performed in MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews. The search was focused on existing systematic reviews addressing each review question, supplemented by other studies published after the time frame covered by the systematic reviews. In phase five data of the included papers were extracted by the surgical resident (RT) and checked by the methodologist (JK) and the GDG. If needed, meta-analysis of the systematic reviews was updated by the surgical resident and the methodologist using Review Manager. During phase six the GDG members decided what recommendations could be made based on the evidence found in the literature using GRADE. Results: There were six sections: (i) symptoms, diagnosis and classification; (ii) basic treatment; (iii) outpatient procedures; (iv) surgical interventions; (v) special situations; (vi) other surgical techniques. Thirty-four recommendations were formulated. Conclusion: This international, multidisciplinary guideline provides an up to date and evidence based summary of the current knowledge of the management of HD and may serve as a useful guide for patients and clinicians