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Purpose: The risk, prevention, and treatment of colorectal neoplasia in inflammatory bowel disease (IBD) are still a matter of debate. The aim of this study was to analyze the occurrence of colorectal neoplasia in IBD patients who underwent proctocolectomy. Methods: The study population comprised of 123 IBD patients who underwent proctocolectomy because of neoplasia, therapy refractivity, or complications between January 2000 and July 2011. Results: One hundred fourteen (92.7 %) patients were pre-operatively diagnosed with ulcerative colitis, 5 (4.1 %) with colitis indeterminata, and 4 (3.3 %) with colonic Crohn's disease. Colectomy was indicated in 39 (31.7 %) patients because of a neoplasia, in 68 (55.3 %) because of a refractory course of the disease, and in 16 (13.0 %) because of complications. Neoplasia was found in 36 patients on a histopathologic evaluation of the colectomy specimens. Ten (8.1 %) patients post-operatively showed a pre-operatively not described advanced neoplasia. In three (2.4 %) of these patients, the detection of advanced neoplasia (two high-grade intraepithelial neoplasias (IENs), one carcinoma) was a complete de novo finding. Carcinoma had not been diagnosed pre-operatively in six (4.9 %) patients. A multifocal distribution of neoplasia was seen in 66.7 % of patients with neoplasia. The median duration of disease was 15.5 years in case of neoplasia opposed to 6.0 years in those without neoplasia detection. Conclusion: Our data demonstrate a high rate of pre-operatively undetected high-grade IENs and carcinoma and a frequent multifocal occurrence in IBD patients with long-standing inflammation of the colon. This should be kept in mind for treatment decisions particularly in patients with a chronic refractory course of the disease. [ABSTRACT FROM AUTHOR]

The article presents abstracts on laboratory medicine which include the use of flow cytometry in the diagnosis of myelodysplastic syndrome (MDS), the significance of DNA methylation in colorectal cancer and the association between skin aging and epigenetic modifications.

Mesenchymal stem cells (MSCs) gain an increasing focus in the field of regenerative medicine due to their differentiation abilities into chondrocytes, adipocytes, and osteoblastic cells. However, it is apparent that the transformation processes are extremely complex and cause cellular heterogeneity. The study aimed to characterize differences between MSCs and cells after adipogenic (AD) or osteoblastic (OB) differentiation at the proteome level. Comparative proteomic profiling was performed using tandem mass spectrometry in data-independent acquisition mode. Proteins were quantified by deep neural networks in library-free mode and correlated to the Molecular Signature Database (MSigDB) hallmark gene set collections for functional annotation. We analyzed 4108 proteins across all samples, which revealed a distinct clustering between MSCs and cell differentiation states. Protein expression profiling identified activation of the Peroxisome proliferator-activated receptors (PPARs) signaling pathway after AD. In addition, two distinct protein marker panels could be defined for osteoblastic and adipocytic cell lineages. Hereby, overexpression of AEBP1 and MCM4 for OB as well as of FABP4 for AD was detected as the most promising molecular markers. Combination of deep neural network and machine-learning algorithms with data-independent mass spectrometry distinguish MSCs and cell lineages after adipogenic or osteoblastic differentiation. We identified specific proteins as the molecular basis for bone formation, which could be used for regenerative medicine in the future. [ABSTRACT FROM AUTHOR]

Purpose: Presently, no markers exist to predict metachronous metastasis at the time a primary colorectal cancer is diagnosed. While aneuploidy indicates poor survival prognosis and elevated carcinoembryonic antigen (CEA) levels the presence of recurrent disease, the predictive value of both markers regarding imminent metachronous metastases is unclear. Methods: Sixty patients with distant recurrence throughout a 5-year follow-up (TM+) were randomly chosen and 60 patients without metastasis matched to this cohort (TM−). In addition, an enlarged collective ( n = 217; n = 85, n = 132) with median follow-up of 79.2 months was assessed by logistic regression regarding metachronous metastases. Univariate and stepwise regression analyses included clinicopathological characteristics, preoperative CEA levels and aneuploidy assessed by DNA image cytometry. Results: The matched-pair collective showed aneuploidy in 71.1 % (TM−) and 85.0 % (TM+; p = 0.076), and elevated CEA in 24.5 % (TM−) and 52.2 % [TM+; odds ratio (OR), 3.414; p = 0.007]. The enlarged collective presented aneuploidy in 71.2 % (TM−) and 83.5 % (TM+; OR 2.050, p = 0.038), and elevated CEA in 28.6 % (TM−) and 48.9 % (TM+; OR 2.391, p = 0.020). Elevated CEA and aneuploidy did not show any association ( p = 0.919). In contrast, logistic regression analyses demonstrated that besides increased T category (OR 1.745, p = 0.019), both elevated CEA level (OR 2.633, p = 0.015) and aneuploidy (OR 1.929, p = 0.058) were independent predictive markers for metachronous metastasis. Conclusions: Our data show that aneuploidy and elevated CEA levels besides increased T category could serve for individual risk assessment to predict metachronous metastases. The fact that still aneuploidy missed the significance level by a small margin emphasizes the need for larger validation studies. [ABSTRACT FROM AUTHOR]

DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa ( n = 19), diploid ( n = 31), and aneuploid ( n = 47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers. [ABSTRACT FROM AUTHOR]

Microtubule-stabilizing (MTS) agents, such as taxanes, are important chemotherapeutics with a poorly understood mechanism of action. We identified a set of genes repressed in multiple cell lines in response to MTS agents and observed that these genes are overexpressed in tumors exhibiting chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival" genes is associated with poor outcome in estrogen receptor-positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane resistance but carboplatin sensitivity, indicating that CIN may determine MTS response in vivo. Thus, pretherapeutic assessment of CIN may optimize treatment stratification and clinical trial design using these agents. [ABSTRACT FROM AUTHOR]

Background and Purpose: To this day, the diagnostic and therapeutic strategy for acute lower gastrointestinal hemorrhage requiring transfusion varies among different hospitals. The purpose of this paper was to evaluate our own data on the group of patients presented and to outline our diagnostic and therapeutic regime taking into account the literature of the past 30 years.Methods: Following prospective data collection on 63 patients of a university hospital (40 male, 23 female patients) who received surgical intervention for acute lower intestinal hemorrhage requiring transfusion, we retrospectively analyzed the data. After a medical history had been taken, all patients underwent clinical examination, including digital palpation; 62 patients underwent procto-rectoscopy, 38 gastroscopy and colonoscopy, 52 patients colonoscopy only, and 45 patients gastroscopy only. Angiography was applied in 14 cases and scintigraphy in 20 cases.Results: Diagnostic procedures to localize hemorrhage were successful in 61 cases, 41 of which through endoscopy, 12 through angiography, and eight through scintigraphy. Of our group of patients, 32 suffered from a bleeding colonic diverticulum, eight from angiodysplasia, and five from bleeding small bowel diverticula. Five patients had inflammatory bowel disease and three neoplasia. Among the surgical interventions, segmental resections were performed most frequently (15 sigmoidectomies, 11 small bowel segmental resections, 11 left hemicolectomies, seven right hemicolectomies, one proctectomy). Subtotal colectomies were carried out in ten cases. The complication rate for this group of critically ill, negatively selected patients was 60.3% and the mortality rate was 15.9%.Conclusions: Examination and stabilization of the patient is directly followed by diagnostic localization. Today, we primarily rely on nonsurgical control of hemorrhage by endoscopy or angiography; the indication for surgery is mainly limited to peracute, uncontrollable, and recurrent forms. In the case of surgery, intestinal segmental resection is recommended after identification of the lesion; if the localization of colonic hemorrhage is uncertain, subtotal resection is the method of choice. For stable patients with unverifiable small-bowel hemorrhage we recommend regular re-evaluation. [ABSTRACT FROM AUTHOR]

B Change in Author Names b In the original version of our article [[1]], insufficient acknowledgement was given for the proteomic experiments, sample selection, analysis of results and drafting of the manuscript. B Change in the Authors Contributions b Due to the change in the author list, the Author contributions were corrected in the original article version [[1]]. All authors read as well as approved the final manuscript and agreed to be personally accountable for the author's own contributions. [Extracted from the article]