Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients.

PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients.     

Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells.

PURPOSE: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. EXPERIMENTAL DESIGN: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). RESULTS: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. CONCLUSIONS: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.     

A comparison of forward and inverse treatment planning for intensity-modulated radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: To compare intensity-modulated treatment plans of patients with head and neck cancer generated by forward and inverse planning. MATERIALS AND METHODS: Ten intensity-modulated treatment plans, planned and treated with a step&shoot technique using a forward planning approach, were retrospectively re-planned with an inverse planning algorithm. For this purpose, two strategies were applied. First, inverse planning was performed with the same beam directions as forward planning. In addition, nine equidistant, coplanar incidences were used. The main objective of the optimisation process was the sparing of the parotid glands beside an adequate treatment of the planning target volume (PTV). Inverse planning was performed both with pencil beam and Monte Carlo dose computation to investigate the influence of dose computation on the result of the optimisation. RESULTS: In most cases, both inverse planning strategies managed to improve the treatment plans distinctly due to a better target coverage, a better sparing of the parotid glands or both. A reduction of the mean dose by 3-11Gy for at least one of the parotid glands could be achieved for most of the patients. For three patients, inverse planning allowed to spare a parotid gland that had to be sacrificed by forward planning. Inverse planning increased the number of segments compared to forward planning by a factor of about 3; from 9-15 to 27-46. No significant differences for PTV and parotid glands between both inverse planning approaches were found. Also, the use of Monte Carlo instead of pencil beam dose computation did not influence the results significantly. CONCLUSION: The results demonstrate the potential of inverse planning to improve intensity-modulated treatment plans for head and neck cases compared to forward planning while retaining clinical utility in terms of treatment time and quality assurance.     

Urgent and emergency carotid TEA

Restoration of blood flow to reperfuse ischemic but not infarcted areas of the brain (ischemic penumbra) and the removal of an ongoing embolic source are the therapeutic aims of emergency and urgent carotid endarterectomy (CEA), both in patients with an acute or progressive ischemic stroke and in patients in the early period after a carotid-related stroke. Based on poor results in the 60ies and 70ies, many centers traditionally perform CEA four to six weeks after a carotid-related stroke at the earliest interval. Since natural history is associated with a high risk of an disabling and/or recurrent stroke in several subgroups of patients, some reports were able to show that urgent and emergency CEA could be worthwhile in well-selected patients.     

Does the architecture of hospital facilities influence nosocomial infection rates? A systematic review.

OBJECTIVE: To review the evidence regarding the effects of interventions to improve hospital design and construction on the occurrence of nosocomial infections. METHODS: Systematic review of experimental and non-experimental, architectural intervention studies in intensive care units (ICUs), surgical departments, isolation units, and hospitals in general. The studies dated from 1975, and were in English, French, German, Italian, and Spanish. Regardless of format, the studies were identified through seven medical databases, reference lists, and expert consultation. RESULTS: One hundred seventy-eight scientific articles were identified; however, none of these described a meta-analysis, systematic review, or randomized, controlled trial. Most of the articles were categorized at the lowest level of evidence (expert judgment or consensus statements). Only 17 described completed concurrent or historical cohort studies matching the inclusion criteria (ICUs, 9; surgical departments, 4; isolation units, 2; hospitals in general, 2). The interventions generally included a move to other premises or renovation. However, in many studies, the staff-to-patient ratio was also improved. Some studies showed lower infection rates after intervention, but this finding cannot be generalized because of confounding and frequently small study populations. CONCLUSIONS: The lack of stringent evidence linking hospital design and construction with the prevention of nosocomial infection is partly attributable to the multifactorial nature of these infections, and some improvement will be seen if basic conditions such as the availability of sufficient space, isolation capacity, and facilities for handwashing are met. However, to our knowledge, other factors, especially the improper hand hygiene of medical staff, have greater impact.     

Are the children of fatherless families more frequently emotionally disturbed in adult life?

It has been the subject of numerous debates recently whether children who grew up without fathers suffer more than others under the long-term consequences of their fatherless childhood. In 1994 we conducted a large-scale population-based investigation over a hundred subjects who had grown up without father to establish standardized norms for various psychometric questionnaires that were also relevant to this issue. This allows us to contribute to the discussion with some concrete data, which correspond without exception with the dominant trend of other research results. Whereas there was evidence to support the view that some children of fatherless families do indeed suffer from increased emotional disturbance in later life, there were also indications that others even profited emotionally from their fatherless childhood. In the area of bodily complaints the results were confounded to a high degree with gender differences, showing that women are more frequently negatively affected, and men more positively.     

The Antonovsky Sense of Coherence Scale. Test statistical evaluation of a representative population sample and construction of a brief scale

In this article we will describe the evaluation of Antonovsky's 29-items Sense of Coherence Scale (SOC-29) in a large community sample (n = 2.005) of the German population and the development of the Leipzig Short Scale (SOC-L9), which consists of only 9 items. The SOC-29 has a high internal consistency (alpha = 0.92), however, the SOC-subscales (comprehensibility, manageability, meaningfulness) were correlated with each other. A principal component factor analysis did not identify the 3-factor structure of the SOC-Scale. It appears that the best solution consists of one global factor. The newly developed SOC-L9, conceptualized as an unidimensional scale, is a reliable and valid instrument, which allows to assess the SOC economically. In our study the Sense of Coherence depended on age and gender. Women and older people reported a lower SOC. Furthermore we found significant associations between SOC and different subjective health measures. A high SOC was associated with both a lower extent of subjective body complaints and somatoform symptoms and with minor health-related problems in daily living.     

Angiogenesis in ischemic human myocardium: clinical results after 3 years

BACKGROUND: Using the human fibroblast growth factor we could already demonstrate the induction of neoangiogenesis in the ischemic human myocardium. METHODS: Forty patients, who were undergoing elective coronary artery bypass grafting were randomly selected and allotted either to a treatment or a control group. In 20 patients (study group) fibroblast growth factor was injected directly into the myocardium, close to the left anterior descending coronary artery. The control group comprised 20 patients who had been injected with heat denatured fibroblast growth factor. The 3-year follow-up consisted of a clinical examination, echocardiography, and selective imaging of the internal mammary artery bypass using angiography. RESULTS: As with the early results, a dense new capillary network could be demonstrated angiographically in the region where the factor had been injected. Echocardiography showed an increase in the left ventricular ejection fraction in the study group. We also found a more pronounced improvement in the clinical appearance of the patients with fibroblast growth factor. CONCLUSIONS: Fibroblast growth factor, in addition to operative myocardial revascularization, may be the appropriate treatment for patients with peripheral stenosis or diffuse coronary arteriosclerosis. It is necessary to confirm these results in further studies on a larger group of patients.