Differential survival trends of stage II colorectal cancer patients relate to promoter methylation status of PCDH10, SPARC, and UCHL1.

Surgical excision of colorectal cancer at early clinical stages is highly effective, but 20-30% of patients relapse. Therefore, it is of clinical relevance to identify patients at high risk for recurrence, who would benefit from adjuvant chemotherapy. The objective of this study was to identify prognostic and/or predictive methylation markers in stage II colorectal cancer patients. Therefore, we selected six gene promoters (FZD9, PCDH10 (protocadherin 10), SFRP2, SPARC (secreted protein acidic and rich in cysteine), UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), and WIF1) for methylation analysis in formalin-fixed, paraffin-embedded primary tumor samples of colorectal cancer patients (n=143) who were enrolled in a prospective randomized phase III trial of the Austrian Breast and Colorectal cancer Study Group. Patients were randomized to adjuvant chemotherapy with 5-fluorouracil and leucovorin or surveillance only. Survival analyses revealed that combined evaluation of three promoters (PCDH10, SPARC, and UCHL1) showed differential effects with regard to disease-free survival and overall survival in the two treatment groups (significance level 0.007). In the chemotherapy arm, a statistically insignificant trend for patients without methylation toward longer survival was observed (P=0.069 for disease-free survival and P=0.139 for overall survival). Contrary, patients in the surveillance arm without methylation in their gene promoters had shorter disease-free survival and overall survival (P=0.031 for disease-free survival and P=0.003 for overall survival), indicating a prognostic effect of methylation in this group (test for interaction, P=0.006 for disease-free survival and P=0.018 for overall survival). These results indicate that promoter methylation status of PCDH10, SPARC, and UCHL1 may be used both as prognostic and predictive molecular marker for colorectal cancer patients and, therefore, may facilitate treatment decisions for stage II colorectal cancer.

Adjuvant sequencing of tamoxifen and anastrozole is superior to tamoxifen alone in postmenopausal women with low proliferating breast cancer.

PURPOSE: To assess the predictive value of Ki67 expression in postmenopausal hormone receptor-positive early-breast cancer patients, who were either treated with adjuvant tamoxifen (TAM) alone or with TAM followed by anastrozole (ANA). EXPERIMENTAL DESIGN: Expression of Ki67 was determined centrally by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospectively randomized Austrian Breast and Colorectal Cancer Study Group Trial 8, and had received TAM for 5 years, or TAM for 2 years followed by ANA for 3 years. Ki67 expression was evaluated both as a continuous variable and dichotomized to low (≤10%) and high (>10%). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic parameters. RESULTS: Patients with a high Ki67 expression (394/1,587; 23%) had a significantly shorter RFS (adjusted HR for recurrence = 1.90, 95% CI: 1.37-2.64, P = 0.0001) and OS (adjusted HR for death = 1.78, 95% CI: 1.18-2.70, P = 0.006). In women with breast tumors expressing medium or high ER levels (n = 1,438), the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS (P = 0.03). TAM followed by ANA was superior to TAM alone in patients with low Ki67 (adjusted HR = 0.53, 95% CI: 0.34-0.83, P = 0.005) but not in high Ki67 disease (adjusted HR = 1.18, 95% CI: 0.66-1.89, P = 0.68). CONCLUSIONS: Adjuvant sequencing of TAM and ANA is superior to TAM alone, particularly in postmenopausal women with medium or high ER expressing, low proliferating breast cancer.

22-Gb/s Long Wavelength VCSELs.

1.55-microm vertical cavity surface-emitting low-parasitic lasers show open eyes up to 22-Gb/s modulation speed. Uncooled error-free operation over a wide temperature range up to 85 degrees C under constant bias conditions is demonstrated at 12.5-Gb/s data rate. At these fixed bias conditions the laser characteristics are practically invariant with temperature. These are the highest data-rates reported from a long-wavelength VCSEL structure to date.

Localized fibrous tumors (LFTs) of the pleura: clinical data, asbestos burden, and syntactic structure analysis applied to newly defined angiogenic/growth-regulatory effectors.

This study was performed to add clinical data, to introduce new markers, and to perform syntactic structural analysis on localized fibrous tumors (LFTs) of the pleura. The material comprised clinical data and processed sections obtained from 36 patients. The results achieved from quantitative imaging techniques and syntactic structure analysis were correlated with clinical data, including patients' habits (smoking), asbestos exposure, survival, and tumor recurrence. The disease caused increasing chest pain and dyspnea in 47% of patients. Exposure to asbestos was noted in 13 out of 36 patients, whereas smoking posed no major risk factor. Two patients developed a recurrent tumor after 8 and 42 months, respectively; none of the other patients died of this tumor disease within the follow-up period of maximal 212 months. The cases were clearly discriminated from mesotheliomas by the marker profile. Frequent expression of accessible ligands for endogenous lectins galectins-1 and -3, the expression of the angiogenic macrophage migration inhibitory factor (MIF), and the dense vascularization intimate a functional relationship. The proliferation index (Nv) was computed to be 1.6% in line with the balance of galectin expression. Abnormal p53 was expressed in only 19.4% of the cases. The diagnosis of LFT can be aided by quantitative assessment of vimentin, CD34, MIF, vascularization, and proliferation. Considering the galectin network, differential expression was noted with preference to effectors limiting growth and aggressiveness.

Long-wavelength tunable vertical-cavity surface-emitting lasers and the influence of coupled cavities.

In this paper, we present an InP-based micromechanically tunable VCSEL emitting in the 1.55microm wavelength region with a 26nm tuning range. The laser is based on a two-chip concept, allowing for a separate optimization of the curved top mirror and the amplifying component. Current confinement is achieved by a buried tunnel junction. The design of the microcavity ensures fundamental mode operation with a side mode suppression ratio exceeding 49dB even for large apertures. Simulations indicate that the tuning range is limited by coupled cavity effects and reveal important design criteria like an upper boundary regarding the device thickness.

The clinical diagnostic accuracy rate regarding the immediate cause of death in a hospitalized geriatric population; an autopsy study of 1594 patients.

BACKGROUND: In the geriatric population the autopsy rate is low, leading to mortality statistics often based on clinical diagnoses alone. OBJECTIVES: To determine the clinical diagnostic accuracy rate regarding the immediate cause of death (CDARCD), the number of major underlying diseases and sole diagnoses, and general data about the immediate cause of death in geriatric hospitalized patients. METHODS: The autopsy proven immediate cause of death was compared with the clinical diagnosis in 1594 patients over 69 years of age. Based on the autopsy protocols, the mean number of major underlying diseases and sole diagnoses were calculated. The immediate cause of death was classified into six groups: cardiovascular disease (CVD), malignant neoplasms (MN), bronchopulmonary disease (BPD), fatal pulmonary embolism (PE), miscellaneous (M), and marantic atrophy (MA). RESULTS: The overall CDARCD was 52.5%, being highest in MN (65.0%), followed by CVD (56.0%), MA (50%), BPD (48.3%), M (44.3%), and PE (26.7%). The most common cause of death was CVD (35.8%), followed by MN (24.3%), BPD (19.8%), PE (10.6%), M (7.7%) and MA (1.9%). The mean number of major underlying diseases and sole diagnoses was 2.0 and 14.4 respectively. CONCLUSIONS: The low CDARCD in our study strongly indicates the need for autopsy when reliable mortality statistics are desired.

Successful hip arthroplasty using cementless titanium implants in rheumatoid arthritis.

Over a period of eight years, we implanted a total of 76 cementless hip prostheses in patients with rheumatoid arthritis. The clinical results of 47 patients (70 hips) increased from a mean Harris Hip Score of 33 to 85 after an average of 49 months (range 1-11 years). One threaded cup has had to be revised because of loosening, and one stem because of femoral fracture. At the latest follow-up, 88% of Hofer-Imhof threaded cups had complete bone ingrowth (Type 0); 10% had near-complete bone ingrowth with minimal radiolucency in one third of the bone contact area (Type 1), and 2% had radiolucency in two thirds of the bone contact area (Type 2). Hemispherical push-in cups showed significantly more radiolucency around the cup. For the stems (Uni, Zweymüller SL), 83% showed no radiolucency (Type 0); 17% had radiolucency only very proximally (Type 1). Minor remodelling (Type 1) occurred in 60% of the femoral shafts; 30% had moderate femoral density loss (Type 2), and 10% had severe bone loss and cortical thinning (Type 3). There was no correlation between marked shaft atrophy and clinical symptoms. With regard to radiolucency and remodelling, there was no significant difference between the two types of stem used. Cementless hip arthroplasty using titanium implants has an excellent outcome in the medium term.

Developmental regulation of presence of binding sites for neoglycoproteins and endogenous lectins in various embryonic stages of human lung, liver and heart.

Protein-carbohydrate interactions are supposed to play key roles in the mechanisms of cell adhesion, biosignalling and intracellular routing, warranting the analysis of the developmental course of expression of epitopes of this system. Thus, a panel of carrier-immobilized carbohydrate ligands was used as probes, namely lactose,N-acetylgalactosamine,N-acetylglucosamine, mannose, fucose and maltose. Additionally, an antibody to an endogenous ß-galactoside-binding lectin (anti-galectin-1), the biotinylated lectin and two further human lectins, namely the macrophage migration inhibitory factor-binding sarcolectin and serum amyloid P component (SAP) that displays selectivity for sulphated sugars and mannose-6-phosphate, were included. They enabled us to assess the extent of the presence of respective binding sites in fixed sections from human lungs (pulmonary epithelial cells), livers (hepatocytes) and hearts (myocard cells) of 10-50 weeks gestation. Invariably, specific binding was detected in the three organ types, at least in certain stages. In most of the cases, the intensity of staining exhibited developmental regulation. The apparent patterns reveal similarities between the different cell types, as seen with immobilizedN-acetylglucosamine as well as with labelled galectin-1 and sarcolectin. However, drastic differences among such patterns with nearly opposite developmental courses do also occur, as detected for carrier-attached mannose and maltose residues. These results point to a potential importance for the detected glycohistochemical features in human development and substantiate the possibility of differential regulation of the presence of binding sites for distinct sugars within a certain organ and between the individual cell types of the monitored organs.