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Life-threatening acute aortic dissection (AD) demands timely diagnosis for effective intervention. To streamline intrahospital workflows, automated detection of AD in abdominal computed tomography (CT) scans seems useful to assist humans. We aimed at creating a robust convolutional neural network (CNN)-based pipeline capable of real-time screening for signs of abdominal AD in CT. In this retrospective study, abdominal CT data from AD patients presenting with AD and from non-AD patients were collected (n 195, AD cases 94, mean age 65.9 years, female ratio 35.8%). A CNN-based algorithm was developed with the goal of enabling a robust, automated, and highly sensitive detection of abdominal AD. Two sets from internal (n = 32, AD cases 16) and external sources (n = 1189, AD cases 100) were procured for validation. The abdominal region was extracted, followed by the automatic isolation of the aorta region of interest (ROI) and highlighting of the membrane via edge extraction, followed by classification of the aortic ROI as dissected/healthy. A fivefold cross-validation was employed on the internal set, and an ensemble of the 5 trained models was used to predict the internal and external validation set. Evaluation metrics included receiver operating characteristic curve (AUC) and balanced accuracy. The AUC, balanced accuracy, and sensitivity scores of the internal dataset were 0.932 (CI 0.891-0.963), 0.860, and 0.885, respectively. For the internal validation dataset, the AUC, balanced accuracy, and sensitivity scores were 0.887 (CI 0.732-0.988), 0.781, and 0.875, respectively. Furthermore, for the external validation dataset, AUC, balanced accuracy, and sensitivity scores were 0.993 (CI 0.918-0.994), 0.933, and 1.000, respectively. The proposed automated pipeline could assist humans in expediting acute aortic dissection management when integrated into clinical workflows., Competing Interests: Declarations. Ethics Approval: This retrospective study was approved by the local institutional review board (2021–635). Written informed consent was not required due to the retrospective nature of the study population enrolled. Competing Interests: SOS: the Department of Radiology and Nuclear Medicine has general research agreements with Siemens Healthineers. FGZ: the Department of Computer Assisted Clinical Medicine has general research agreements with Siemens Healthineers. Others: no conflicts of interest declared., (© 2024. The Author(s).)

Elevated high-sensitivity cardiac troponin (hs-cTn) levels should be expected in about half of all patients with acute ischemic stroke (AIS). Since those patients are at risk of increased morbidity and mortality, often attributable to cardiac causes, an adequate work-up of the underlying etiology is required. This can only be achieved by a team of cardiologists and neurologists. Since underlying causes of hs-cTn elevation in AIS patients are diverse, often atypical or silent in their clinical presentation and some, such as an accompanying myocardial infarction, can be acutely life-threatening, the work-up should follow a standardized clinical algorithm. The vast majority of hs-cTn elevations are caused by non-ischemic myocardial injury associated with AIS. This work presents a practice-oriented approach to differential diagnosis with the update of the Mannheim clinical algorithm for acute ischemic stroke and troponin elevation., (© 2024. The Author(s).)

Objective: The aim of the study is to assess the correlation between artificial intelligence (AI)-based low attenuation volume percentage (LAV%) with forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) and visual emphysema grades in routine chest computed tomography (CT). Furthermore, optimal LAV% cutoff values for predicting a FEV1/FVC < 70% or moderate to more extensive visual emphysema grades were calculated., Methods: In a retrospective study of 298 consecutive patients who underwent routine chest CT and spirometry examinations, LAV% was quantified using an AI-based software with a threshold < -950 HU. The FEV1/FVC was derived from spirometry, with FEV1/FVC < 70% indicating airway obstruction. The mean time interval of CT from spirometry was 3.87 ± 4.78 days. Severity of emphysema was visually graded by an experienced chest radiologist using an established 5-grade ordinal scale (Fleischner Society classification system). Spearman correlation coefficient between LAV% and FEV1/FVC was calculated. Receiver operating characteristic determined the optimal LAV% cutoff values for predicting a FEV1/FVC < 70% or a visual emphysema grade of moderate or higher (Fleischner grade 3-5)., Results: Significant correlation between LAV% and FEV1/FVC was found (ϱ = -0.477, P < 0.001). Increasing LAV% corresponded to higher visual emphysema grades. For patients with absent visual emphysema, mean LAV% was 2.98 ± 3.30, for patients with trace emphysema 3.22 ± 2.75, for patients with mild emphysema 3.90 ± 3.33, for patients with moderate emphysema 6.41 ± 3.46, for patients with confluent emphysema 9.02 ± 5.45, and for patients with destructive emphysema 16.90 ± 8.19. Optimal LAV% cutoff value for predicting a FEV1/FVC < 70 was 6.1 (area under the curve = 0.764, sensitivity = 0.773, specificity = 0.665), while for predicting a visual emphysema grade of moderate or higher, it was 4.7 (area under the curve = 0.802, sensitivity = 0.766, specificity = 0.742). Furthermore, correlation between visual emphysema grading and FEV1/FVC was found. In patients with FEV1/FVC < 70% a high proportion of subjects had emphysema grade 3 (moderate) or higher, whereas in patients with FEV1/FVC ≥ 70%, a larger proportion had emphysema grade 3 (moderate) or lower. The sensitivity for visual emphysema grading predicting a FEV1/FVC < 70% was 56.3% with an optimal cutoff point at a visual grade of 4 (confluent), demonstrating a lower sensitivity compared with LAV% (77.3%)., Conclusions: A significant correlation between AI-based LAV% and FEV1/FVC as well as visual CT emphysema grades can be found in routine chest CT suggesting that AI-based LAV% measurement might be integrated as an add-on functional parameter in the evaluation of chest CT in the future., Competing Interests: S.O.S. has a cooperation with Siemens-Healthineers, which does not bias the content of the manuscript. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Low attenuation volume percentage (LAV%) has been identified as a quantitative imaging biomarker for emphysema with good correlation with spirometry. The influence of intravenous contrast agent on LAV% and its correlation with spirometry is not well known., Purpose: To evaluate the influence of intravenous contrast agent on artificial intelligence (AI)-based LAV% in correlation with spirometric Tiffeneau-Pinelli Index (TI)., Material and Methods: In a retrospective study, two groups of 47 patients (mean age 68.04 ± 12.64 and 67.89 ± 11.54 years) with either non-enhanced chest computed tomography (CT) or contrast-enhanced CT were compared. Using an AI-based software, LAV% was quantified using a threshold <-950 HU. TI was calculated from spirometry and pathologic airway obstruction was considered with a TI <70. The effect of contrast agent on LAV% and the relationship between TI and LAV% was analyzed. Correlation coefficients between TI and LAV% were compared for both groups., Results: Patients with non-enhanced CT had a mean LAV% of 9.07 ± 7.53. Of them, 22 patients had a TI <70% and 25 patients a TI ≥70%. Patients with contrast-enhanced CT had a mean LAV% of 6.54 ± 4.62. Of them, 20 patients had a TI <70% and 27 patients had a TI ≥70%. Contrast agent did not show a major effect on LAV% ( P  = 0.099) and the relationship between TI and LAV% ( P  = 0.88). In both groups, a significant correlation between TI and LAV% was found (ρ = -0.317 for non-enhanced CT; ρ = -0.514 for contrast-enhanced CT). Difference between correlation coefficients was insignificant., Conclusion: Our findings suggest that contrast agent does not influence LAV% nor its correlation with TI.

Background: Acute lower respiratory infection (ALRI) is a major cause of morbidity and mortality worldwide in young children and is predominately caused by viral respiratory pathogens. This study aims to identify the viral etiologies of ALRI in hospitalized children in Jordan University Hospital and compare the clinical characteristics of influenza virus infection with other respiratory viruses., Methods: A retrospective viral surveillance study that included 152 children below 15 years of age admitted with ALRI from December 2018 through April 2019 was conducted. We recorded results of real-time reverse transcriptasepolymerase chain reaction (RT-PCR) for common respiratory viruses. Clinical and demographic information of the study population was collected from patients' electronic medical records., Results: 152 patients were identified with a median age of 1 year (mean was 2.1 years). Ninety-five patients (62.5%) were males. One or more viral respiratory pathogens were detected in 145 (95.3%) children. Respiratory syncytial virus was the most detected virus in 68 patients (44.8%). Influenza virus was detected in 25 patients (16.4%). Children with influenza infection had more fever and lower leukocyte count compared to children infected with other viruses. The severity of the ALRI correlated significantly with several factors, including age less than six months and the presence of neuromuscular disease (p<0.05)., Conclusion: Viral detection was common among children admitted with ALRI. Viruses, including influenza, are recognized as significant contributors to the morbidity associated with ALRI. More attention is needed on strategies for the prevention and detection of viral ALRI in developing countries., (©Copyright: the Author(s).)

We report 24 patients with holoprosencephaly (HPE) spectrum screened for Del 7q36 and subtelomere 13q. They were divided according to the type of HPE into: 6 alobar, 15 semilobar, 1 lobar and 2 middle interhemispheric variant (MIH). All patients presented with global developmental delay. Microcephaly was in 83.3% and midfacial developmental defects were in the form of; cyclopia, arrhinia and agnathia in 2 patients (8.3%), premaxillary agenesis in 2 patients (8.3%), cleft lip and palate in 7 patients (29.2%), hypotelorism in 8 patients (33.3%) and hypertelorism in 9 patients (37.5%). The neurological deficits were as follows: abnormal tone and spasticity were present in all of them with exceptional of a single patient with MIH who presented with hypotonia and was able to walk independently at the age of 3 years, athetoid and/or dystonic movements of limbs in 22 patients, seizures in twelve patients (50%) and abnormal EEG in 15 patients (62.5%). Poor temperature regulation was found in 50% of patients and diabetes insipidus was documented in 3 patients (12.5%). The MRI showed complete or partial fusion of basal ganglia and thalami in 21 patients (87.5%) and 19 patients (79.2%) respectively, fused mesencephalon in 8 patients (33.3%), incomplete separation of mesencephalon from diencephalon in 4 patients (16.7%), dorsal cyst in 10 patients (41.7%), abnormal gyral pattern anteriorly in 15 patients (62.5%), anterior located sylvian fissures in 22 patients (99.7%), complete or partial agenesis of the corpus callosum (ACC) in all patients and Dandy-Walker malformation (DWM) in three patients (12.5%). A small occipital cephalocele was detected clinically and radiological as atretic type in MIH patient. Karyotype analysis demonstrated 47, XY+13 in a patient with alobar holoprosencephaly, 46, XY,t(12;13) (q13q24.1;q14q33) in a semilobar case associated with DWM, 46, XY, del(13)(q34) in one semilobar case and three cases had del 7q36 using FISH technique in two semilobar cases and one lobar case. Conclusion: This study highlights the clinical spectrum in patients with HPE and report a case of HPE and DWM associated with t(12;13). Neuroimaging delineated the pathogenesis underlying developmental defects in HPE. Accurate molecular diagnosis is crucial for further understanding of the pathogenesis of HPE.

Introduction: Chronic lymphocytic leukemia (CLL) is a clonal lymphoproliferative disorder characterized by progressive accumulation of morphologically and immunophenotypically mature lymphocytes. Characterization of genomic aberrations may help to understand the pathogenesis of CLL and may give prognostic information independent from conventional clinical markers for a risk-adapted management of CLL patients., Aim: The aim of the present study is to determine the most common cytogenetics abnormalities between patients with CLL and its prognostic impact., Patients and Methods: The present study was carried out on 20 adult patients presented with chronic lymphocytic leukemia. The patients were diagnosed on the basis of standard clinical (lymph node involvement and/or hepatosplenomegaly), hematological and immunophenotypic criteria for diagnosis of B-CLL. All cases were studied at the time of their diagnosis. FISH technique was successfully performed on PB samples using CLL LSI probes for ATM (11q22) / GLI (12q13) and 13q14/ p53 (17p13)., Results: For comparative statistical studies, the patients were divided into group I (patients with favorable outcome) and group II (patients with unfavorable outcome). All patients showed one or more cytogenetic abnormality with the prevalence of p53 in 16 patients out of 20 that perfectly correlated with the poor outcome of the patients. This is followed by deletion in the 13q14 and to a lesser extent deletion in ATM gene, but no one has exhibited amplification in the 12q13 locus., Conclusion: p53 deletion as a sole abnormality has a higher prognostic power than other cytogenetics abnormalities. The cytogenetics study using FISH panel for CLL patients in a complementary fashion to the other clinical and laboratory findings may overcome the pitfalls in the diagnosis and may also assess the assignment of therapeutic protocols for CLL patients according to the results of their cytogenetic analysis at the time of diagnosis., Keywords: FISH, chronic lymphocytic leukemia, CLL, p53, cytogenetics, Egypt.

Rationale and Objectives: To quantitatively assess coronary atherosclerotic plaque composition in patients with acute non-ST elevation myocardial infarction (NSTEMI) and patients with stable coronary artery disease (CAD) by coronary computed tomography angiography (cCTA) correlated with virtual histology intravascular ultrasound (VH-IVUS)., Materials and Methods: Sixty patients (35 with NSTEMI) were included. Corresponding plaques were assessed by dual-source cCTA and VH-IVUS regarding volumes and percentages of fatty, fibrous, and calcified component; overall plaque burden; and maximal percent area stenosis. Possible differences between patient groups were investigated. Concordance between cCTA and VH-IVUS measurements was validated by Bland-Altman analysis., Results: Forty corresponding plaques (22 of patients with NSTEMI) were finally analyzed by cCTA and VH-IVUS. cCTA plaque analysis revealed no significant differences between plaques of patients with NSTEMI and stable CAD regarding absolute and relative amounts of any plaque component (fatty: 20 mm³/13% versus 17 mm³/14%; fibrous: 81 mm³/63% versus 80 mm³/53%; calcified: 16 mm³/14% versus 26 mm³/26%; all P > .05) or overall plaque burden (153 mm³ versus 165 mm³; P > .05), nor did VH-IVUS plaque analysis. VH-IVUS measured a higher area stenosis in patients with NSTEMI compared to patients with stable CAD (76% versus 68%, P = .01; in cCTA 69% versus 65%, P = .2). Volumes of fatty component were measured systematically lower in cCTA, whereas calcified and fibrous volumes were higher. No significant bias was observed comparing volumes of overall noncalcified component and overall plaque burden., Conclusion: Plaques of patients with acute NSTEMI and of patients with stable CAD cannot be differentiated by quantification of plaque components. cCTA and VH-IVUS differ in plaque component analysis., (Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Muscle invasive bladder cancer has a mortality rate at 5 years of 50%, despite radical therapy, as a result of tumour progression and dissemination. This suggests that half of patients have disseminated disease at the time of diagnosis, which is not detected by the staging techniques currently used. The prognostic factors (histological grade and tumour stage) and current staging techniques do not discriminate between those patients who will be cured with surgical treatment and those who will die from metastatic spread. New diagnostic and prognostic tools that complement the existing methods and provide a proper assessment of carcinoma invading bladder muscle are therefore essential. Molecular staging techniques using specific biomarkers have been applied in various solid tumours to determine the presence of missed tumour cells in lymph nodes (LNs) during routine pathological examination. These techniques could identify patients with LN micrometastases who may potentially benefit from early treatment with chemotherapy. This study compares the performance of conventional histological analysis and molecular biomarkers in detecting bladder cancer LN micrometastases and predicting patient's clinical outcome. The study found that, even though a clear trend to a worse outcome was shown in those patients who became node-positive after molecular analysis, no statistical differences were found in cancer-specific and recurrence-free survival analysis between those patients who were negative by histology but positive by molecular analysis and those who were negative by both techniques. We concluded that molecular analysis of LN spreading in bladder cancer has a better detection rate than conventional histological examination., Objective: • To improve the sensitivity of histological examination in detecting occult lymph node (LN) dissemination of bladder cancer using gene expression analysis., Patients and Methods: • We carried out a retrospective study that included 504 formalin-fixed paraffin-embedded LNs from 90 patients with muscle invasive bladder cancer and 35 controls. • Gene expression values of two molecular biomarkers (FXYD3 and KRT20) were analysed using reverse transcription real-time quantitative PCR (RT-qPCR). • Molecular results were compared with histological status and patients' clinical outcomes., Results: • Of the 90 patients analysed, 16 were positive and 74 were negative by histological analysis. Of these 74, 19 were classified as positive using RT-qPCR. • Significant differences in cancer-specific (P= 0.011) and recurrence-free (P= 0.009) survival were found between the three patient groups (patients positive by both techniques, patients negative by both techniques, and patients negative by histological but positive by molecular analysis). • A significant difference was not found between histologically negative but molecularly positive patients and patients who were negative by both techniques, but a clear trend to a worse outcome was found in those patients who became node-positive after molecular analysis., Conclusions: • The analysis of FXYD3 and KRT20 could improve current pathological examination for the detection of micrometastases in LNs. • Further and more extensive studies will determine the real prognostic value of such LN micrometastases., (© 2012 BJU INTERNATIONAL.)

Objectives: We analyzed the effects of anti-hedgehog signaling on the (18)F-FDG uptake of pancreatic cancer xenografts (PCXs) using a clinically implemented positron emission tomography (PET)-computer tomography (CT) scanner with high-resolution reconstruction., Methods: PCXs from two pancreatic cancer cell lines were developed subcutaneously in nude mice and injected intraperitoneally with a low dose of cyclopamine for 1 week. (18)F-FDG PET-CT was performed using a new-generation clinical PET-CT scanner with minor modifications of the scanning protocol to adapt for small-animal imaging. The data set was reconstructed and quantified using a three-dimensional workstation., Results: MiaPaCa-2 cells, which respond to cyclopamine, showed decreased (18)F-FDG uptake without a change in tumor size. For hip tumors, the maximum standardized uptake value (SUV(max)) was reduced by -24.5 ± 9.2%, the average SUV (SUV(avg)) by -33.5 ± 7.0%, and the minimum SUV (SUV(min)) by -54.4 ± 11.5% (P < .05). For shoulder tumors, SUV(max) was reduced by -14.7 ± 7.5%, SUV(avg) by -12.6 ± 6.3, and SUV(min) by -30.3 ± 16.7% (P < .05). Capan-1 cells, which do not respond to cyclopamine, did not show significant SUV changes., Conclusions: The new generations of clinically implemented PET-CT scanners with high-resolution reconstruction detect a minimal response of PCX to low-dose short-term cyclopamine therapy without changes in tumor size and offer potential for preclinical translational imaging.

Objective: To compare different CT acquisition techniques regarding for attenuation-based characterization of coronary atherosclerotic plaques using histopathology as the standard of reference., Materials and Methods: In a post mortem study 17 human hearts were studied with dual-source CT (DSCT) and dual energy CT (DECT) mode on a DSCT as well as with 16-slice single-source CT (SSCT). At autopsy, atherosclerotic lesions were cut at 5 μm sections. Histopathologic classification of the plaques according to the American Heart Association (AHA) criteria was performed by two pathologists. Attenuation values of all plaques were measured in DSCT, DECT and SSCT studies, respectively and classified based on attenuation according to modified AHA criteria., Results: 58 coronary plaques were identified at autopsy. Regardless of the CT technique only 52/58 plaques were found at CT (sensitivity=89.6%). There was no significant difference between the mean attenuation values of different plaque types between DSCT, DECT, and SSCT: type IV: 11HU/8HU/19HU; type Va: 44HU/45HU/52HU; type Vb: 1088HU/966HU/1079HU). The sensitivity for correct classification varied depending on the plaque type (type II=0%, type III=0%, type IV=43%, type Va=58%, Vb=97%)., Conclusion: Independent of the used acquisition technique, SSCT, DSCT and DECT show similar results for attenuation-based characterization of atherosclerotic coronary plaques., (Copyright © 2010. Published by Elsevier Ireland Ltd.)

Objective: FXYD-3, also known as Mat-8, is a member of the FXYD protein family. It was reported that this protein can associate with and modify the transport properties of Na, K-ATPase, and may play an important role in a variety of physiological and pathological states. This protein is up-regulated in certain types of cancers (such as breast, prostate and pancreatic cancer), but down-regulated in other types of cancers (such as colon and kidney cancer). No study has been performed in gastric cancer; therefore, the aim of this project was to investigate FXYD-3 expression and its clinicopathological significance in gastric adenocarcinoma., Patients and Methods: FXYD-3 protein was examined by immunohistochemistry in normal gastric mucous (n= 29) and gastric adenocarcinoma (n=51), obtained from surgical resection of gastric cancer patients., Results: FXYD-3 protein was present in the cytoplasm of normal gastric epithelial cells or gastric cancer cells. The rate of FXYD-3 strong expression was significantly higher in cancer (51% of 51) than in normal mucosa (10% of 29, X;{2}=13.210, p < 0.0001). FXYD-3 expressed strongly in ulcerative/infiltrating types of cancers compared to polypoid/fungating ones (X;{2}=5.765, p=0.016). However, FXYD-3 expression was not correlated with patient's gender, age, tumor size, lymph node status and histological grade (p > 0.05). Conclosion: Up-regulated expression of FXYD-3 protein may be involved in tumourgenesis and invasion of gastric adenocarcinoma.

We report a case of chronic lymphocytic leukemia with a characteristic cytogenetics finding detected by fluorescent in situ hybridization. This case has deletion in p53 gene in 50% of interphase nuclei studied in the peripheral blood and polyploidy in 30% of cells. To our knowledge polyploidy is not commonly reported with chronic lymphocytic leukemia patients.

Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables., Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immunohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36)., Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0 .02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to be increased compared with normal mucosa regardless of RT., Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.

FXYD3, interacting with Na+/K+-ATPase, is considered a cell surface regulator modulating the function of ion pumps and ion channels. The FXYD3 gene was originally cloned from murine mammary tumors and then from human breast tumors. However, no study of FXYD3 has been carried out in gliomas; therefore, we examined FXYD3 expression in gliomas and its clinicopathological significance. FXYD3 expression was immunohistochemically examined in 71 primary gliomas, along with 37 matched adjacent normal brain samples and 8 recurred gliomas. The frequency of strong FXYD3 expression was higher in the primary tumors in either unmatched (p = 0.046) or matched cases (p = 0.02), compared to normal brain tissue. FXYD3 expression was significantly more increased in females than males (p = 0.01), and in multiple site gliomas than single sites (p = 0.02). There was no difference of FXYD3 expression regarding age, tumor location, size, histological type, and tumor grade (p > 0.05). The results suggest that FXYD3 expression may be involved in glioma development, especially in multiple gliomas and female patients.

Aim: The diversity in the aggressiveness of cystic tumors of the pancreas - ranging from the usually benign serous cystadenoma to lesions of variable degrees of malignancy - was utilized for the identification of molecular factors that are involved in the occurrence of malignancy., Methods: We analyzed the transcript profiles of different cystic tumor types. The results were confirmed at the protein level by immunohistochemistry. Also, functional studies with siRNA silencing were performed., Results: Expression variations at the RNA and protein level were identified that are closely correlated with the degree of malignancy. Besides, all tumors could be classified effectively by this means. Many of the identified factors had not previously been known to be associated with malignant cystic lesions. siRNA silencing of the gene with the most prominent variation - the anti-apoptotic factor FASTK (Fas-activated serine/threonine kinase) - revealed a regulative effect on several genes known to be relevant to the development of tumors., Conclusion: By a molecular analysis of rare types of pancreatic cancer, which are less frequent in terms of disease, variations could be identified that could be critical for the regulation of malignancy and thus relevant to the treatment of also the majority of pancreatic tumors., (Copyright 2008 S. Karger AG, Basel and IAP.)

Background: FXYD3 is up-/down-regulated in different types of cancers. We examined FXYD3 expression in colorectal cancers and its relationship to biological and clinicopathological variables., Patients and Methods: Expression of FXYD3 protein was immunohistochemically examined in distant normal mucosa (n = 34), adjacent normal mucosa (n = 72), primary tumour (n = 150) and lymph node metastasis (n = 35) from colorectal cancer patients., Results: FXYD3 was highly expressed in primary tumour compared to adjacent normal mucosa (p = 0.02). FXYD3 was or tended to be positively related to the expression of ras (p = 0.02), p53 (p = 0.06), legumain (p = 0.02) and proliferating cell nuclear antigen (p = 0.03). Moreover, there was a higher frequency of strong FXYD3 expression in Dukes A-C tumours than in D tumours (p = 0.04). The strong FXYD3 expression tended to predict worse survival in the patients with Dukes A + B tumour (p = 0.07), while there was no such tendency in the patients with Dukes C + D tumour (p = 0.94). The tumours located in the colon had a higher degree of FXYD3 expression than the tumours located in the rectum (p = 0.05)., Conclusion: The FXYD3 was associated with certain biological variables and may be involved in the development of the relative earlier stages of colorectal cancers., (Copyright 2009 S. Karger AG, Basel.)

Background: The Shwachman-Bodian-Diamond syndrome (SBDS) protein is a member of a highly conserved family which influences RNA activation and is associated with pancreatic, skeletal and bone marrow deficiencies, as well as hematological malignancies., Methods: In this study, the expression and localization of SBDS were investigated in normal human pancreatic tissues, chronic pancreatitis (CP) tissues, primary and metastatic pancreatic ductal adenocarcinoma (PDAC) tissues, as well as in cultured pancreatic cancer cell lines by immunohistochemistry, immunoblotting and immunocytochemistry., Results: In the normal pancreas, SBDS was localized in the cytoplasm of islet cells and ductal cells. In CP tissues, SBDS was found in the cytoplasm of ductal cells, tubular complexes, stromal fibroblasts and in PanIN1-2 lesions. In PDAC tissues, SBDS exhibited cytoplasmic and occasionally nuclear localization in tubular complexes, PanIN1-3 lesions, cancer cells, and stromal fibroblasts. Different levels of SBDS protein were detected in cultured pancreatic cancer cell lines., Conclusion: SBDS is expressed in normal, CP, and PDAC tissues, as well as in pancreatic cancer cell lines. The different expression and localization patterns suggest a role of SBDS in the pathogenesis of, or response to, inflammatory and neoplastic pancreatic diseases.

Jacobsen syndrome is a rare disorder, caused by segmental monosomy for the distal end of the long arm of chromosome 11 with variable phenotypic expressivity. We report on the first male (6 years old) and female (3 years old) sibs with clinical and cytogenetics characterization of Jacobsen syndrome. Their karyotypes showed deletion 11q23.3-qter. Patients presented with growth and psychomotor retardation, facial dysmorphism, eye anomalies, and congenital heart disease (variable degrees of septal defect). Family history revealed a clinically similar brother, who died at 2 months old from cardiac anomalies in the form of single ventricle without being subjected to further investigations. Chromosomal analysis of the parents was normal. Karyotyping for the 2 patients and their parents was confirmed by fluorescence in situ hybridization analysis (FISH) using whole chromosome painting probes for 11 (WCP 11). Relevant investigations for both sibs showed mild thrombocytopenia with normal platelets morphology and striking periventricular demyelination on neuroimaging. Inguinal small testicles as well as focal epileptiform dysfunction were recorded in the male patient only. Abdominal ultrasound, hearing test, and DEXA scan were normal in both patients. Due to of the presence of apparently 3 affected offspring and normal parental karyotypes, an inherited predisposition was highly suspected. The large size of the distal deleted 11q segment in our patients support the recent hypothesis, that Jacobsen syndrome is a chromosomal deletion syndrome with genetic predisposition, due to expansion of p(CCG)n trinucleotide in the folate-sensitive fragile site FRA11B, at breakpoint 11q23.3. In conclusion, identification and further delineation of more similar patients will contribute to understanding the genetic basis of the 11q phenotype.

ONECUT1 (HNF-6) is the prototype of a new class of homeodomain transcription factors, that controls the development of pancreatic ducts during mouse development. In the present study, the role of ONECUT1 and its targeted genes TCF2, PKHD1 and CYS1 was analyzed in human pancreatic ductal adenocarcinoma (PDAC). mRNA levels of ONECUT1, TCF2, PKHD1 and CYS1 were measured in pancreatic tissues and pancreatic cancer cell lines by quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR). Protein expression of ONECUT1 and TCF2 was assessed in pancreatic tissues by immunohistochemistry. ONECUT1 was transfected into Panc-1 and T3M4 pancreatic cancer cells and its effects on anchorage-dependent and -independent growth as well as invasion and adhesion were analyzed. Median mRNA levels of ONECUT1, TCF2, PKHD1 and CYS1 were 7.7-, 2.0-, 5.7- and 3.8-fold higher in normal tissues than in PDAC tissues. ONECUT1 protein was expressed in normal acinar and ductal cells, but neither in the cancer cells of PDAC tissues nor in 7 of 8 cultured pancreatic cancer cell lines. There was a significant positive correlation between ONECUT1 and TCF2, CYS1, and PKHD1 mRNA levels in PDAC tissues. Transfection of ONECUT1 into pancreatic cancer cells resulted in up-regulation of the target gene TCF2, a reduction in invasiveness, but no change in adhesion or growth. In conclusion, ONECUT1 expression is lost in pancreatic cancer cells, suggesting a tumor suppressor function in this malignancy.

Background: Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin) is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP), and pancreatic ductal adenocarcinoma (PDAC) using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules., Results: Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells., Conclusion: BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.