Accuracy evaluation of image registration and segmentation tools used in conformal treatment planning of prostate cancer.

Segmentation and registration tools are commonly used in radiotherapy for target and at risk organs localisation. In this work the performances of three different segmentation tools and of a surface matching registration technique, used on computed tomography (CT) and magnetic resonance (MR) images for the treatment planning of conformal prostate carcinoma, are studied. The accuracy of the segmentation and registration tools was evaluated by phantom experiment and on patient data, respectively. A preliminary estimate of MR image distortion was also performed.     

Upregulation of basic fibroblast growth factor in smokers with chronic bronchitis.

The aim of the study was to investigate the expression of basic fibroblast growth factor (bFGF) and its receptor, fibroblast growth factor receptor (FGFR)-1, in the central airways of smokers with chronic bronchitis. The lobar bronchi from 17 subjects undergoing thoracotomy for solitary nodules were examined. All had a history of cigarette smoking, nine had symptoms of chronic bronchitis and airflow limitation, and eight were asymptomatic with normal lung function. Using immunohistochemical methods, bFGF and FGFR-1 expression in the total airway wall and the different airway compartments, i.e. bronchial glands, submucosal vessels and smooth muscle, was quantified. Moreover, to investigate the role of bFGF in angiogenesis, the number of submucosal vessels was quantified. Smokers with chronic bronchitis had an increased bFGF expression in the total airway wall compared with asymptomatic smokers, which was mainly due to bFGF upregulation in bronchial glands. By contrast, the expression of FGFR-1 and the number of submucosal vessels was similar in the two groups of subjects examined. In conclusion, smokers with chronic bronchitis have an increased expression of basic fibroblast growth factor in the central airways, which is mainly due to an increased expression in bronchial glands, suggesting the involvement of this growth factor in the pathogenesis of chronic bronchitis.     

LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space

The pleural space is a virtual compartment between the lung and chest wall that becomes filled with fluid and inflammatory cells during a variety of respiratory diseases. Here, we study the potential role of the eicosanoid metabolite leukotriene B4 (LTB4) in disparate diseases leading to acute (pneumonia) or chronic (tuberculosis, cancer) inflammation of the pleural space. LTB4 concentrations were significantly higher in pleural fluid due to pneumonia, tuberculosis and cancer with respect to congestive heart failure and correlated with neutrophil elastase, which is used as an indication of state of activation of neutrophils in the pleural space. Moreover, pleural LTB4 was biologically active, as an anti-LTB4 antibody partially neutralized the chemotactic activity of parapneumonic, tuberculous and cancer effusions. Macrophages, neutrophils, lymphocytes, mesothelial cells and cancer cells all expressed mRNA for 5-lipoxygenase, the enzyme that initiates leukotriene synthesis leading to the production of LTB4, in exudative pleural effusions. Upon stimulation in transudative pleural effusions, pleural macrophages produced, in a time-dependent fashion, a significantly higher concentration of LTB4 than mesothelial cells. These studies demonstrate that different cell types are capable of producing LTB4 in the inflamed pleural space and that this mediator may play a crucial role in the recruitment of neutrophils into the pleural space.     

A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1, tumor necrosis factor (TNF) and interferon ]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1 and TNF were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a morphological classification for the in vitro studies of pancreatic cancer.     

Airway remodelling in the pathogenesis of asthma

The inflammatory and remodelling processes that underlie asthma result from a highly complex interaction between various cell types. Apart from inflammatory cells, such as eosinophils, activated T cells, mast cells and macrophages, structural tissue cells such as epithelial cells, fibroblasts and smooth muscle cells can also play an important effector role through the release of a variety of mediators, cytokines and chemokines. This results in an acute inflammatory response that is characterized by vascular leakage, mucus hypersecretion, epithelial shedding and widespread airway narrowing. At the same time, through the release of mediators, cytokines, chemokines and growth factors, epithelial and mesenchymal cells cause persistence of the inflammatory infiltrate and induce structural changes in the airway wall, such as increased thickness of the basement membrane, increased collagen deposition, changes in bronchial microcirculation, and smooth muscle hypertrophy and hyperplasia. The end result of airway inflammation and remodelling is an increased thickness of the airway wall, leading to a reduced baseline airway calibre and exaggerated airway narrowing.     

Cow’s Milk Protein Allergy as a Model of Food Allergies

Cow’s milk allergy (CMA) is one of the most common food allergies in infants, and its prevalence has increased over recent years. In the present paper, we focus on CMA as a model of food allergies in children. Understanding the diagnostic features of CMA is essential in order to manage patients with this disorder, guide the use of an elimination diet, and find the best moment to start an oral food challenge (OFC) and liberalize the diet. To date, no shared tolerance markers for the diagnosis of food allergy have been identified, and OFC remains the gold standard. Recently, oral immunotherapy (OIT) has emerged as a new therapeutic strategy and has changed the natural history of CMA. Before this, patients had to strictly avoid the food allergen, resulting in a decline in quality of life and subsequent nutritional, social, and psychological impairments. Thanks to the introduction of OIT, the passive approach involving rigid exclusion has changed to a proactive one. Both the heterogeneity in the diagnostic process among the studies and the variability of OIT data limit the comprehension of the real epidemiology of CMA, and, consequentially, its natural history. Therefore, well-planned randomized controlled trials are needed to standardize CMA diagnosis, prevention, and treatment strategies.     

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score

Annals of Surgical Oncology - Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX? (ODX) recurrence scores has been...     

Choice of neurosurgical approach in the treatment of cranial base lesions

The authors describe a series of surgical approaches that they found particularly useful for the exposure and removal of lesions involving the skull base. These are: 1) fronto-naso-orbital approach; 2) frontotemporo-orbito-zygomatic approach; 3) subtemporal transpetrosal approach; 4) temporo-suboccipital transpetrosal approach (retrolabyrinthine presigmoid; transsigmoid; translabyrintine amend transcochlear presigmoid); 5) dorsolateral approach to the foramen magnum and lower clivus.As the approaches are complex and carry potential risks of morbidity, not only it is important to have a good knowledge of basic anatomy but also to closely follow the indications for each one. In this type of surgery where it is often difficult to achieve complete removal of the lesion by a single route of attack, more than one approach may be employed in different surgical steps. Finally, all these approaches demand extremely scrupulos surgical reconstruction to avoid dangerous postoperative complications that may jeopardize the previous work of the surgeon.     

Sex- and age-related nephrotoxicity due to 1,2-dichloropropane in vitro

Sex- and age-related nephrotoxicity due to 1,2-dichloropropane was studied in vitro by means of renal cortical slices obtained from Wistar rats. Reduced glutathione content, organic anion accumulation (p-aminohippurate), and release of malondialdehyde (to measure the extent of lipid peroxidation), aspartate aminotransferase, -glutamyltransferase and lactate dehydrogenase into the incubation medium were determined. Sex differences in naive rats parameters were slight, but male were more susceptible to toxic effects of 1,2-dichloropropane than female rats; glutathione depletion, lipid peroxidation, and loss of organic anion accumulation were higher in male than in female slices. During senescence, naive male rats showed a progressive decrease of glutathione content (statistically significant from 7–9 months of age), increase of spontaneous lipid peroxidation from the same age, and increase of signs of cytotoxicity (release of aspartate aminotransferase and lactate dehydrogenase into the incubation medium) from 3–4 months of age. A loss of organic anion accumulation started from 7–9 months of age. Slices from rats of 3–4 months old showed the apparently highest susceptibility to 1,2-dichloropropane but depletion of glutathione content and loss of organic anion accumulation were at the same level in the oldest rats. The age decrease of control values caused the differences in the percentage ratio and then, apparently, a lower DCP effect. On the contrary, the increase of aspartate aminotransferase released in the incubation medium by DCP-treated slices corresponded to the age-related increase in cytotoxicity.The work was presented in part to the 1st National Conference of the Molecular and Cellular Toxicology Group, Siena 30. 11.–1.12.1990.