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The aim of this study was to assess the preventive potential of major lifestyle risk factors for acute myocardial infarction (AMI) in middle-aged men. Among 10,981 men in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition, aged 40.2-65.8 years when recruited, 378 developed first-ever AMI during a median follow-up period of 11.4 years. Current smoking, excess body weight, being physically inactive, but not high alcohol consumption, were identified as the major lifestyle risk factors for AMI using Cox regression analysis. A competing AMI risk model built from cause-specific Cox regression models and considering the risk of death predicted 353 AMI cases, 182 (51.6%) of which were estimated as preventable through adherence to a healthy lifestyle profile (never smoking, normal body weight, physically active, and moderate alcohol consumption). The calculated age-specific 5-year incidence rates for AMI in the actual cohort and in a hypothetical, comparable cohort with all men following the healthy lifestyle profile were 128 and 39, respectively, per 100,000 person-years for the age group 40-44, increasing to 468 and 307 per 100,000 person-years for the age group 65-69. The estimated AMI incidence rates for men with the healthy lifestyle profile are still somewhat higher than the average rates reported for documented low-incidence regions, such as parts of Japan. Our analysis confirms the strong primary preventive potential for AMI based on avoidance of smoking and excess body weight, and on regular physical activity.

Purpose: The aim of this study was to evaluate and compare sublobar resection plus intraoperative seed implant (IOS) versus stereotactic body radiation therapy (SBRT) in patients with single malignant lung nodules in patients 70 years of age or older., Materials and Methods: A retrospective chart review was performed and 47 patients with adequate information were selected for analysis. Thirty patients with single malignant lung nodules received SBRT. Seventeen patients received limited surgical resection plus radioactive seed implantation for solitary malignant lung nodules. Univariate statistical analysis showed a significant difference only for the age in the 2 groups: the mean age in the radioactive seed group, 78.8 years versus 76.1 years in the SBRT group (2-sided, P=0.05)., Results: There was high local control and minimal toxicity with either treatment modality and no significant difference among the 2 groups in terms of local control, survival, and toxicity. However, the distant failure was higher but not statistically significant in the SBRT group (9 of 30 patients in SBRT vs. 0 of 17 in IOS, P=0.1)., Conclusions: Our study has shown excellent outcomes and limited toxicity in both IOS and SBRT for treatment of single malignant lung nodules in patients who are not candidates for lobectomy. However, a randomized trial is needed in this group of elderly patients to determine the most appropriate treatment.

In this study, we investigated the mechanism(s) of altered expression of protooncogene SKP2 in metastatic melanoma and its clinical relevance in patients with metastatic melanoma. The genomic status of SKP2 was assessed in cell lines by sequencing, single nucleotide polymorphism array, and genomic PCR. Copy number status was then evaluated for concordance with SKP2 mRNA and protein expression. SKP2 protein was further evaluated by immunohistochemistry in 93 human metastatic tissues. No mutations were identified in SKP2. Increased copy number at the SKP2 locus was observed in 6/14 (43%) metastatic cell lines and in 9/22 (41%) human metastatic tissues which was associated with overexpression of SKP2 protein. Overexpression of SKP2 protein in human tissues was associated with worse survival in a multivariate model controlling for the site of metastasis. Copy number gain is a major contributing mechanism of SKP2 overexpression in metastatic melanoma. Results may have implications for the development of therapeutics that target SKP2., (© 2010 John Wiley & Sons A/S.)

Objective: Previous melanoma studies evaluating prognostic factors of survival at recurrence have focused on primary tumor characteristics and clinical variables at first recurrence. We examined the prognostic relevance of recurrent tumor proliferation., Methods: 114 melanoma patients with available recurrent tissues who were prospectively enrolled at New York University Medical Center were studied. Standard of care prognostic variables (e.g. stage at initial diagnosis and lactate dehydrogenase level) and recurrent tissue expression of proliferative marker Ki-67 were evaluated for their association with overall survival., Results: High Ki-67 expression was observed in 57 (50%) of the 114 recurrent melanomas. On univariate analysis, the median overall survival of patients whose recurrent tumors overexpressed Ki-67 was significantly shorter than that of patients whose recurrent tumors had low Ki-67 expression (3.6 vs. 9.5 years, p = 0.03). On multivariate analysis, a high proliferative index of the recurrent melanoma remained an independent predictor of worse overall survival, controlling for stage at initial diagnosis, disease-free survival, and stage at first recurrence [HR = 2.09 (95% CI 1.24-3.54), p = 0.006]., Conclusions: Our results demonstrate the prognostic relevance of tumor proliferation in recurrent melanoma patients. Data also support restratification of risk assessment upon recurrence that considers tumor biology in addition to clinical variables evaluated as part of the standard of care., (Copyright © 2011 S. Karger AG, Basel.)

Background: The objective of this study was to compare the outcomes of patients who underwent wedge resection plus intraoperative brachytherapy versus patients who received stereotactic body radiotherapy (SBRT) for single malignant lung nodules., Methods: A retrospective chart review included 55 patients who were treated for single lung nodules, and 47 of those patients who had adequate information were chosen for the current analysis. Twenty-five patients with single malignant lung nodules received SBRT. Twenty-two patients underwent limited surgical resection plus radioactive seed implantation for solitary malignant lung nodules., Results: Univariate statistical analysis demonstrated a significance difference only for age in the 2 groups: The mean age in the radioactive seed group (66.6 years) was statistically significantly different from the mean of the age in the SBRT group (75.9 years; 2-sided P=.04). No significant differences were observed between the 2 groups in terms of local control, distant metastasis, survival, or toxicity., Conclusions: The current results demonstrated comparable efficacy in outcome and toxicity between surgical resection with radioactive seed implantation and SBRT for the treatment of single malignant lung nodules in patients who were not candidates for lobectomy/pneumonectomy., (Copyright © 2010 American Cancer Society.)

Background: Emerging data show that patients with operable, HER-2/neu overexpressed/amplified breast carcinomas have significantly better responses (more frequently obtaining pathologic complete response and greater percent disease-free survival) when treated with trastuzumab (Herceptin) simultaneously with neoadjuvant chemotherapy than with chemotherapy alone. With the increasing use of neoadjuvant therapies, clinicians require information on biomarkers including HER-2/neu status at the time of needle core biopsy. Concordance rates between fluorescence in situ hybridization (FISH)-determined HER-2/neu status on needle core biopsies and on subsequent excisional biopsies of the same tumor have not been well studied. Moreover, the practice of automatically performing ("reflexing") 2+ immunohistochemical (IHC) staining needle core biopsies for FISH analysis on the same sample needs to be validated. In this study, we set out to (1) determine the accuracy of HER-2/neu status as determined by FISH on needle core biopsy material compared with FISH on the subsequent excisional biopsy of the same tumor with special consideration of IHC 2+staining cases and (2) determine the constancy of HER-2/neu status in pre-neoadjuvant and post-neoadjuvant chemotherapy-treated tumor in the form of needle core biopsy and excisional biopsy samples, respectively., Design: 100 patients whose needle core biopsies and subsequent excisional biopsy samples were pathologically evaluated at our institution were studied. For each patient, unstained sections from both specimens were prepared and used for IHC or FISH. IHC was carried out using the HercepTest kit (DAKO, Carpinteria, CA). Parallel unstained slides were used to carry out FISH (dual probe, Vysis). Statistical analyses were carried out on the resulting data generated after interpretation., Results: The concordance rate between FISH results determined on the needle core biopsy and subsequent excisional biopsy of the same tumor was 86% (kappa=0.56, P=2x10). If equivocal FISH cases (> or =1.8 to < or =2.2 amplification ratio) in a needle core biopsy or excisional biopsy specimen or both, were excluded, the concordance rate increased to 95% (kappa coefficient=0.86, P=2x10). Fourteen of 100 (14%) cases showed 2+ IHC staining in the needle core biopsy specimen with good concordance of FISH-determined HER-2/neu status between the needle core biopsy and excisional biopsy specimens (79% agreement and kappa=0.512, P=0.05). Nine, 3, and 2 cases of the 14 cases were amplified, equivocal, and negative on the excisional biopsy specimens, respectively. Of the 15 patients who received neoadjuvant chemotherapy, 93% and 87% had no change in HER-2/neu status as determined by IHC or FISH, respectively, in the excisional biopsy specimen when compared with that determined on the prior core biopsy sample., Conclusions: Excellent overall concordance was achieved between FISH-determined HER-2/neu status on the needle core biopsy and that determined on the subsequent excisional biopsy of the same tumor. These results suggest that intratumoral heterogeneity of HER-2/neu assessed by FISH is not a significant confounding factor when analyzing smaller sized samples. Furthermore, 79% of 2+IHC staining needle core biopsy cases showed concordant FISH results in the needle core biopsy and subsequent excisional biopsy specimens. Our results show good concordance, however, larger cohorts need to be studied to verify this finding. HER-2/neu status remains unchanged in the majority of cases when comparing pre-neoadjuvant and post-neoadjuvant chemotherapy-treated specimens.

Chronic mucosal inflammation is considered a risk factor for colorectal cancer. Neutrophils are a major source of oxidants, whereas cyclooxygenase 2 (COX-2) and Hypoxia Inducible Factor-1alpha (HIF-1alpha) protein expression levels are increased in inflammatory and malignant lesions. The main purpose of the present study was to evaluate myeloperoxidase (MPO) positive cell infiltration, COX-2 and HIF-1alpha protein expression in colorectal carcinogenesis, especially in its early phases, using immunohistochemistry and immunofluorescence confocal microscopy techniques. MPO, COX-2 and HIF-1alpha proteins were expressed at higher rates in the normal colorectal mucosa of patients with inflammatory bowel diseases and colorectal tumours than in patients with normal colonoscopy. A gradual increase in COX-2 and HIF-1alpha protein expression was observed in dysplastic aberrant crypt foci, adenomas and carcinomas, showing a strong relation to dysplasia. In conclusion, the present study supports the hypothesis of a key role of inflammation in malignant transformation of colorectal mucosa. The evaluation of some early markers related to inflammation in the mucosa of the large bowel may serve as potential tool for prognosis and therapeutic strategies.

Colorectal mucosa is targeted by toxic agents, which can initiate or promote colon cancer. The mechanism of damage might be a focal irritation with loss of normal epithelial cell barrier function. Genetic alterations in tumors may also affect host inflammatory response. The aim of this study was to define the extent of inflammation in colorectal mucosa, along colorectal carcinogenesis, and in microsatellite stable and unstable colorectal carcinomas. We collected 103 samples of normal colorectal mucosa from 65 patients (35 with colorectal cancer or adenoma, 8 with inflammatory bowel diseases, and 22 controls with normal colonoscopy). We also examined 24 aberrant crypt foci, 14 hyperplastic polyps, 16 adenomas, and 67 samples of colorectal carcinoma. Immunohistochemistry was used to count myeloperoxidase (MPO)-positive cells (neutrophils and monocytes) in x100 optical fields under a light microscope. Patients with colorectal tumors had a higher mean number of MPO-positive cells in normal mucosa than controls (mean +/- SD, 2.7 +/- 2.0 versus 1.4 +/- 1.4; P = 0.017). MPO-positive cell number was tightly linked to dysplasia in aberrant crypt foci and adenomas, and it was higher in carcinomas microsatellite unstable than those microsatellite stable (21.6 +/- 15.5 versus 11.9 +/- 8.0; P < 0.01). MPO immunohistochemistry is a simple and reliable technique for the quantification of inflammation in colorectal mucosa., and it may be a potential marker of colorectal cancer risk. Microsatellite instability seems to influence host immune responses to colorectal carcinoma. These observations strongly support a key role of inflammation in colorectal carcinogenesis.

Background: Neuroblastoma is a malignant condition of the developing sympathetic nervous system that most commonly affects young children and is often lethal. Its cause is not known., Methods: We performed a genomewide association study by first genotyping blood DNA samples from 1032 patients with neuroblastoma and 2043 control subjects of European descent using the Illumina HumanHap550 BeadChip. Samples from three independent groups of patients with neuroblastoma (a total of 720 patients) and 2128 control subjects were then genotyped to replicate significant associations., Results: We observed a significant association between neuroblastoma and the common minor alleles of three consecutive single-nucleotide polymorphisms (SNPs) at chromosome band 6p22 and containing the predicted genes FLJ22536 and FLJ44180 (P=1.71x10(-9) to 7.01x10(-10); allelic odds ratio, 1.39 to 1.40). Homozygosity for the at-risk G allele of the most significantly associated SNP, rs6939340, resulted in an increased likelihood of the development of neuroblastoma (odds ratio, 1.97; 95% confidence interval, 1.58 to 2.45). Subsequent genotyping of the three 6p22 SNPs in three independent case series confirmed our observation of an association (P=9.33x10(-15) at rs6939340 for joint analysis). Patients with neuroblastoma who were homozygous for the risk alleles at 6p22 were more likely to have metastatic (stage 4) disease (P=0.02), amplification of the MYCN oncogene in the tumor cells (P=0.006), and disease relapse (P=0.01)., Conclusions: A common genetic variation at chromosome band 6p22 is associated with susceptibility to neuroblastoma., (2008 Massachusetts Medical Society)

Greenhouse gas (GHG) emissions from post-consumer waste and wastewater are a small contributor (about 3%) to total global anthropogenic GHG emissions. Emissions for 2004-2005 totalled 1.4 Gt CO2-eq year(-1) relative to total emissions from all sectors of 49 Gt CO2-eq year(-1) [including carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O), and F-gases normalized according to their 100-year global warming potentials (GWP)]. The CH4 from landfills and wastewater collectively accounted for about 90% of waste sector emissions, or about 18% of global anthropogenic methane emissions (which were about 14% of the global total in 2004). Wastewater N2O and CO2 from the incineration of waste containing fossil carbon (plastics; synthetic textiles) are minor sources. Due to the wide range of mature technologies that can mitigate GHG emissions from waste and provide public health, environmental protection, and sustainable development co-benefits, existing waste management practices can provide effective mitigation of GHG emissions from this sector. Current mitigation technologies include landfill gas recovery, improved landfill practices, and engineered wastewater management. In addition, significant GHG generation is avoided through controlled composting, state-of-the-art incineration, and expanded sanitation coverage. Reduced waste generation and the exploitation of energy from waste (landfill gas, incineration, anaerobic digester biogas) produce an indirect reduction of GHG emissions through the conservation of raw materials, improved energy and resource efficiency, and fossil fuel avoidance. Flexible strategies and financial incentives can expand waste management options to achieve GHG mitigation goals; local technology decisions are influenced by a variety of factors such as waste quantity and characteristics, cost and financing issues, infrastructure requirements including available land area, collection and transport considerations, and regulatory constraints. Existing studies on mitigation potentials and costs for the waste sector tend to focus on landfill CH4 as the baseline. The commercial recovery of landfill CH4 as a source of renewable energy has been practised at full scale since 1975 and currently exceeds 105 Mt CO2-eq year(-1). Although landfill CH4 emissions from developed countries have been largely stabilized, emissions from developing countries are increasing as more controlled (anaerobic) landfilling practices are implemented; these emissions could be reduced by accelerating the introduction of engineered gas recovery, increasing rates of waste minimization and recycling, and implementing alternative waste management strategies provided they are affordable, effective, and sustainable. Aided by Kyoto mechanisms such as the Clean Development Mechanism (CDM) and Joint Implementation (JI), the total global economic mitigation potential for reducing waste sector emissions in 2030 is estimated to be > 1000 Mt CO2-eq (or 70% of estimated emissions) at costs below 100 US$ t(-1) CO2-eq year(-1). An estimated 20-30% of projected emissions for 2030 can be reduced at negative cost and 30-50% at costs < 20 US$ t(-) CO2-eq year(-1). As landfills produce CH4 for several decades, incineration and composting are complementary mitigation measures to landfill gas recovery in the short- to medium-term--at the present time, there are > 130 Mt waste year(-1) incinerated at more than 600 plants. Current uncertainties with respect to emissions and mitigation potentials could be reduced by more consistent national definitions, coordinated international data collection, standardized data analysis, field validation of models, and consistent application of life-cycle assessment tools inclusive of fossil fuel offsets.

Adenomatous polyposis coli (APC) is a tumor suppressor gene whose main function is the destabilization of beta-catenin, a key effector of the Wnt signaling pathway. This gene is defective in familial adenomatous polyposis (FAP), a dominantly inherited disease, but inactivation of APC has been reported also in most sporadic colorectal tumors and it is considered an early event in colorectal tumorigenesis. The aim of the present study was to evaluate the intracellular ultrastructural distribution of beta-catenin and APC proteins in epithelial cells of normal colorectal mucosa, aberrant crypt foci (ACF, an early premalignant lesion) and cancer. We used the immunogold electron microscopic method to identify both proteins. Normal colonic epithelial cells showed a strong membranous expression of beta-catenin and lacked cytoplasmic and nuclear expression. Normal cells showed APC localization pattern characterized by diffuse nuclear expression and along the plasma membrane. In ACF and in carcinoma an absent or reduced membranous expression of beta-catenin was associated with an increased nuclear and cytoplasmatic expression. In aberrant crypt foci and carcinoma, APC was evident inside the nucleus and at the level of cell-cell junctions, but it was decreased in the cytoplasm. This method allowed the accurate localization of proteins of the Wnt signaling pathway in the early steps of colorectal carcinogenesis. The similar pattern of subcellular distribution of APC and beta-catenin in dysplastic ACF and colorectal cancer suggests that ACF are precursor lesions of sporadic and FAP-associated colorectal carcinoma.

A case of adenocarcinoma of the head of the pancreas in a patient with situs viscerum inversus totalis, an association described for the third time in literature, is reported. The possible coexistence of malformations of transposed organs and the specular anatomosurgical situation requires particular attention in the diagnosis and preoperative evaluation as well as a careful reorientation of the surgical perspective and a correct surgical conduct.

The objective of this study was to assess the radiative forcing due to Finnish anthropogenic greenhouse gas emissions in three scenarios. All the Kyoto Protocol gases, i.e., CO(2), CH(4), N(2)O, and fluorinated gases, were included. The calculations showed that forcing due to Finnish emissions will increase in the case of all gases except methane by the year 2100. In 1990, radiative forcing due to Finland's emission history of all Kyoto Protocol gases was 3.2 mW/m(2), of which 71% was due to carbon dioxide, 17% to methane, and the rest to nitrous oxide. In 1990 the share of fluorinated gases was negligible. The share of methane in radiative forcing is decreasing, whereas the shares of carbon dioxide and of fluorinated gases are increasing and that of nitrous oxide remains nearly constant. The nonlinear features concerning additional concentrations in the atmosphere and radiative forcing due to emissions caused by a single country or activity are also considered. Radiative forcing due to Finnish emissions was assessed with two different approaches, the marginal forcing approach and the averaged forcing approach. The impact of the so-called background scenario, i.e., the scenario for concentration caused by global emissions, was also estimated. The difference between different forcing models at its highest was 40%, and the averaged forcing approach appeared to be the more recommendable. The effect of background concentrations in the studied cases was up to 11%. Hence, the choice of forcing model and background scenario should be given particular attention.

The copper (Cu) resistance of Arctostaphylos uva-ursi was tested in a pot experiment (lasting 8 weeks) using rooted cuttings originating from an area near the Harjavalta Cu-Ni smelter, SW Finland. The fine roots were moderately infected by arbutoid mycorrhizae. The plants were exposed to five Cu levels (1, 10, 22, 46 and 100 mg l(-1)) given repeatedly together with a nutrient solution. The critical Cu concentration in the nutrient solution inhibiting the growth of A. uva-ursi was below 10 mg l(-1) Cu (EC(50) value for biomass production 3.3 mg l(-1) Cu). This concentration was clearly lower than the value we have found earlier for other dwarf shrubs under similar experimental conditions. Most of the Cu given accumulated in the roots and old stems. The results suggest that A. uva-ursi cuttings were relatively sensitive to Cu despite the ability of the adult clones to grow in Cu-contaminated soil. The adult clones extend their roots into the less toxic deeper soil layers, which may facilitate the avoidance of heavy metals.

The purpose of this first level research is to analyze the organization of the treatment of oncological pain in one Italian province. For the data collection a questionnaire was submitted in the Intensive Care Unit to the responsibles and to the staff in the public hospital structures of the six USL of the Nuoro's province. Results prove that the motivation of the staff and their problem sensitivity, are inadequate to guarantee an effective answer to the patient's need. The main aspects are: legal aspect, concerning the district level interventions ache care formation aspect for registered nurses the necessity to adopt quality evaluation methods.

According to the experience of the authors on a non-selected case report, pharmacologic progresses in the therapy of various aspects of peptic disease permit an ease management also of gastro-esophageal reflux disease. Moreover, endoscopy is the very modern pivot of conservative treatment of more severe complications as strictures are, through repetitive and progressive instrumental dilatations. The surgical treatment of the most severe and intractable eveniences must be chosen for only a low percentage number of patients, after a careful functional analysis of the single case. Very important is the endoscopic and histologic control of Barrett esophagus and severe dysplasia.

It has been done a manometric intraoperating study on 18 patients (7 acalasical megaoesophagi, 6 herniae of hiatus, 5 duodenal ulcers) who had undergone an operation of modified Dor's anti-reflux plastics. After Haller H.P.Z. pressure has gone down of 13 mmHg, and has gone up again of 5,5 mmHg after modified Dor; after plastics H.P.Z. average intraoperating pressure has been of 18 mmHg. The posterior plastics of hiatus and the reconstruction of His' angle for hernia of hiatus modify scarcely H.P.Z. pressure. During a superselective vagotomy we have recorded a modest reduction of H.P.Z. pressure, of which average intraoperating values after vagotomy and anti-reflux plastics have been of 16,5 mmHg. At a distance of 30 months from the operation it has been done a follow up on 70% of patients that had undergone an operation of anti-reflux plastics and also 18 patients that had had en intraoperating inspection. However it has been, a degradation of manometric values, the results have been satisfactory over 90% of cases. The authors insist on the utility of intraoperating manometry for a valuation of the completenes and the efficacy of the operation.

After a short preface about the main antireflux techniques employed in the treatment and prevention of gastro-oesophageal reflux, the problems involved in the iatrogenous gastro-oesophageal reflux are stated. As no unanimous opinion exists till now in literature about the importance and incidence of reflux after the operation of extramucous cardiomyotomy according to Heller, used in the treatment of achalasia, and after the Parietal Cell Vagotomy, employed in the treatment of duodenal ulcer, an experimental protocol was set up. An experimental research was performed on 16 dogs, subdivided into 3 groups: in the first group (6 dogs) extramucous cardiomyotomy according to Heller and antireflux procedure (antero-lateral hemifundoplication according to Dor-Casolo) were performed; in the second group (6 dogs) Parietal Cell Vagotomy + extramucous cardiomyotomy according to Heller + antero-lateral hemifundoplication according to Dor-Casolo were performed; in the third group (control) the only extramucous cardiomyotomy according to Heller was performed. In the research, articulated in two stages (1st time - operation; 2nd time - remote checking) the following was effected: pressure gauge test; pH-metric test; gastro-oesophageal scintigraphic test with Tc99m; histopathologic test. The experimental results obtained, elaborated by computer, demonstrated: that extramucous cardiomyotomy according to Heller causes serious oesophagitic phenomena, and therefore it should be joined to antireflux procedure; that Parietal Cell Vagotomy (P.C.V.) causes a significant decrease in the tone of L.E.S. (Lower Oesophageal Sphincter); that antero-lateral hemifundoplication according to Dor-Casolo (210 degrees) is effective in its antireflux action even after long time.

We report the results of a study carried out with cephalexin and bromhexine in a group of 100 patients at risk for bronchopulmonary complications following abdominal surgery. The treatment achieved very good activity and excellent tolerance. We consider this therapy very useful for prophylaxis and treatment of bronchopulmonary complications in patients who have undergone surgery.