Expression of the nuclear bile acid receptor/farnesoid X receptor is reduced in human colon carcinoma compared to nonneoplastic mucosa independent from site and may be associated with adverse prognosis.

The nuclear bile acid receptor/farnesoid X receptor (FXR; NR1H4) is involved in bile acid homeostasis, cell proliferation and apoptosis and has been linked to intestinal carcinogenesis in mice. Aim of this study was to analyze FXR expression in human normal intestinal mucosa and colon carcinoma. We achieved systematic mapping of FXR expression of human intestinal mucosa and analysis of 75 human colon carcinomas using FXR immunohistochemistry on formalin-fixed, paraffin-embedded tissue. FXR expression gradually decreased from terminal ileum to the sigmoid colon with strongest expression in the terminal ileum (p < 0.001). FXR expression in carcinomas was reduced compared to peritumoral nonneoplastic mucosa (p < 0.000). Loss of FXR expression was significantly correlated with grading in tumors of the right colon (p = 0.008). FXR expression in tumor and normal tissue showed an inverse correlation with stage. FXR expression in tumor was inversely correlated with clinical outcome. No association was found with patients' age and sex. In nonneoplastic mucosa FXR expression concurred with low expression of Ki-67. In carcinomas, no association was found between FXR expression and Ki-67 and cyclin D1, respectively. Development of colon carcinoma in humans is associated with reduced FXR expression independent of site and may reflect an impaired defense against potentially carcinogenic bile acids along their intestinal gradient. In contrast to normal colon mucosa, FXR expression in carcinomas is not associated with low proliferation. Colon carcinomas with FXR expression seem to be associated with lower stage and a more favourable outcome compared to FXR negative carcinomas.

Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems.

STUDY DESIGN: Retrospective study. OBJECTIVE: This study analyzed the predictive value of the scoring systems of Bauer, Bauer modified, Tokuhashi, Tokuhashi revised, Tomita, van der Linden, and Sioutos as well as the parameters included in these systems. SUMMARY OF BACKGROUND DATA: Metastases of the spinal column are a common manifestation of advanced cancer. Severe pain, pathologic fracture, and neurologic deficit due to spinal metastases need adequate treatment. Besides oncologic aspects and quality of life, treatment decisions should also include the survival prognosis. METHODS: Two hundred fifty-four patients with confirmed spinal metastases were investigated retrospectively (treatment 1998-2006; 62 underwent surgery and 192 had conservative treatment only). Factors related to survival, such as primary tumor, general condition (Karnofsky Performance Status Scale), neurologic deficit, number of spinal and extraspinal bone metastases, visceral metastases, and pathologic fracture, were analyzed. The survival period was calculated from date of diagnosis of the spinal metastases to date of death or last follow-up (minimum follow-up: 12 months). For statistical analysis, univariate and stepwise multivariate Cox regression analyses were performed. RESULTS: Median overall survival for all patients was 10.6 months. The following factors showed significant influence on survival in multivariate analysis: primary tumor (P < 0.0001), status of visceral metastases (P < 0.0001), and systemic therapy (P < 0.0001). Using the recommended group assignment for each system, only Bauer and Bauer modified showed significant results for the distinction between good, moderate, and poor prognosis. The other systems failed to distinguish significantly between good and moderate prognosis. The hazard ratio of the absolute score of all analyzed systems was, however, statistically significant, with a better score leading to lower risk of death. CONCLUSION: According to this analysis, the Bauer and the Bauer modified scores are the most reliable systems for predicting survival. Since the Bauer modified score furthermore consists of only four positive prognostic factors, we emphasize its impact and simplicity.

Accurate preoperative echocardiography has more impact on prediction of long-term mortality than intra-operatively measured flow in coronary bypass grafts.

OBJECTIVE: Our study aimed to analyze the predictive value of intra-operative bypass graft flow measurements for long-term mortality. METHODS: A total of 1593 consecutive coronary artery bypass graft (CABG) patients routinely underwent intra-operative bypass graft flow measurements with the transit-time flow meter (TTFM: Cardiomed(®)). The results of the flow measurements and the demographics were analyzed retrospectively. RESULTS: The mean follow-up was 3.8 years (0.5-8.8 years) with no losses to follow-up. Overall mortality was 10.1%. The preoperative left ventricular ejection fraction (LVEF) (echocardiograph) was the highest independent predictor of long-term survival (hazard ratio 0.97, p = 0.004) in all groups. The univariate analysis for the CABG I group showed that besides LVEF, female gender (hazard ratio 3.6, p = 0.02) was also significant. For the CABG II group, additive EuroSCORE (European System for Cardiac Operative Risk) (ES) (hazard ratio 1.4, p = 0.0001) and age (hazard ratio 1.1, p = 0.001) were significant. In the CABG III group, ES (hazard ratio 1.2, p < 0.0001), age (hazard ratio 1.04, p = 0.001), IMA (hazard ratio 0.5, p < 0.0001) and concomitant aortic valve replacement (AVR) (hazard ratio 2.1, p = 0.03) were significant, in addition to the LVEF. CONCLUSION: With quality-controlled surgeons checked by intra-operative TTFM, accurate quantification of preoperative LVEF significantly predicts long-term outcome. Effective bypass graft flows failed to predict outcome in CABG patients, regardless of the degree of coronary artery disease (CAD) and concomitant AVR.

Myeloperoxidase as serum marker for detection of CMV infections and rejections in patients after liver or heart transplantation.

Rejection episodes and infections are common problems after organ transplantations (TX). Rejection can be diagnosed in liver-transplant (LTX) patients when liver-specific enzymes in the serum are elevated. As endomyocardial biopsy (EMB) is the gold standard for detecting heart transplant (HTX) rejection, serum parameters would permit more selective use of this invasive procedure. Cytomegalovirus (CMV) infections can have serious consequences for TX patients and so should be diagnosed and treated timely. At present, there are no suitable diagnostic methods other than CMV antigen pp65 and CMV polymerase chain reaction (PCR). Our study aimed to test the sensitivity of myeloperoxidase (MPO), an enzyme of neutrophilic granulocytes, as a new serum parameter in addition to established serum parameters and EMB for diagnosis of infection and rejection episodes after LTX and HTX. MPO in plasma from 246 blood samples (103 used for statistical analysis) from 27 patients (18 LTX and 9 HTX) was determined using ELISA; C-reactive protein (CRP), gamma-glutamyl-transpeptidase (GGT), white blood count and CMV pp65 antigen were monitored routinely. EMBs were performed at defined intervals after HTX. Results were analyzed with descriptive statistics, T-test, Wilcoxon test and Cox regression analysis, whereby a p<0.05 was viewed as significant. MPO values in TX patients with an infection (7 LTX, 2 HTX) were significantly higher than in TX patients without complications (control group) (253.9 microg/l vs. 116.6 microg/l, p=0.0194). In TX patients with rejections (6 LTX, 6 HTX), there is also a significant increase in comparison to controls (429.7 microg/l vs. 116.6 microg/l, p=0.0001). Data from individual TX patients, however, indicate that MPO levels rise distinctly earlier with infection (CMV) than with rejection, enabling earlier detection of the complication and initiation of suitable treatment. Our findings suggest that a larger and prospective study should be designed to evaluate the usefulness of MPO levels in assessing organ transplant recipients.

Serum Epstein-Barr virus DNA load in primary Epstein-Barr virus infection.

Specific viral laboratory diagnosis of primary Epstein-Barr Virus (EBV) infection is usually based on antibody-detection assays. During acute, lytic phase of infection, viral DNA can also be detected in serum. In the present study, the diagnostic utility of EBV DNA detection and quantitation in serum in primary EBV infection was investigated. The level of EBV DNA in the serum of 98 immunocompetent patients aged 1-47 years with symptomatic, antibody-confirmed EBV primary infection was assessed using a quantitative real-time PCR assay. The association between viral load and time after onset of disease, age and clinical and laboratory data was investigated. Quantitative PCR detected EBV DNA in 93 of 98 samples (94.9%), and the measured viral loads ranged from 3.8 x 10(1) to 6.6 x 10(4) copies/ml. EBV DNA detection exhibited a sensitivity of 94.9% and a specificity of 97.4% for primary EBV infection. EBV DNA was always detectable until day 12 after onset of symptoms, whereas no further positive PCR results were found after a period of 22 days after onset of disease. Detection of EBV DNA also showed a clearer association with the clinical manifestation of disease than the presence of EBV specific VCA IgG antibodies of low avidity. EBV DNA load was found to correlate inversely with the time after onset of disease (P < 0.001), and higher viral load levels were detected in younger (P = 0.009) and in hospitalized patients (P = 0.038). The results indicate that real-time PCR is a reliable tool for diagnosis of primary EBV infection early in the course of disease. In addition, EBV DNA detection may serve as a useful diagnostic supplement in serologically indeterminate EBV infections.