Is there a role for adjuvant therapy in radiation-induced angiosarcoma of the breast? A case report and review of the literature.

BACKGROUND: Angiosarcoma (AS) of the breast is very rare, accounting for 1% of all soft tissue breast tumors. AS may present as primary tumors of the breast or as secondary lesions usually associated with previous radiotherapy. Commonly, secondary AS affects older women (median age 67-71 years) with a clinical history of breast cancer. The preferred site of onset of RIAS is the edge of radiation fields, where radiation doses and tumor necrosis may be heterogeneous, resulting in a DNA damage and instability. Radical surgery is the treatment of choice, but no clear consensus exists on surgical management of breast AS. CASE REPORT: We describe an atypical case of relapsed RIAS after radical mastectomy, treated with new surgery and, considering the higher risk of recurrence, subsequent adjuvant chemotherapy with weekly paclitaxel. CONCLUSIONS: The frequency of radiation-induced angiosarcomas (RIAS) after breast-conserving surgery and radiotherapy has been increased to 0.14-0.5% among long survivors. Nevertheless, even if RIAS continues to be prognostically an extremely unfavorable cancer due to a high rate of recurrence, distant spread, and median overall survival (OS) of about 60 months, the benefits of loco-regional breast radiotherapy are clearly higher than the risk in developing angiosarcoma.

Elective Treatment of Large-Bowel Obstruction in Asymptomatic Sigmoid Volvulus.

BACKGROUND: Sigmoid volvulus is an uncommon cause of intestinal obstruction representing the 5% of all Western cases, associated with old age and a history of neurological and psychiatric condition. Generally, its diagnosis is established by clinical and radiologic findings. It often represents an emergency and it is commonly associated with pain, vomit and abdominal tenderness. CASE PRESENTATION: We present a case of a 59 years old man, admitted to our emergency department, showing an abdominal X-Ray reporting a distention of large bowel,which was required due to presence of multiple diarrhea episodes during the previous 7 days. He had no significant past medical history and did not report constipation or subocclusive episode. CONCLUSIONS: Volvulus should be considered in the differential diagnosis in adult and healthy patients with bowel obstructions. Surgery is, in all cases, the radical and definitive treatment since there is a higher mortality in case of recurrent volvulus. Despite the massive bowel distention, our choice was the elective open surgery. Primary anastomosis is feasible and safe and did not lead to any complications. In case of unsuccessful colonic decompression, evidence to support or refute the safety and effectiveness of laparoscopic surgical resection for treatment of patients with sigmoid volvulus disease is not yet proven.

Perineal trauma with anal avulsion: case report.

Anorectal avulsion is an exceptional rectal trauma. In this kind of lesions, the anus and the sphincter no longer join the perineum and are pulled upward. We present a case of 34-years-old patient who was admitted because of a pelvic-perineal trauma, presenting a partial anorectal avulsion, exposed femoral fracture with thigh's lacerated-contused wound. Our treatment included primary plastic of the internal anal sphincter with replanting of the rectum on the anal canal and a diverting loop sigmoid colostomy (SCS), so as to prevent sepsis. Closure of the protective SCS was performed four months after the trauma.

Incidental Diagnosis of a Rare Case of Corkscrew Aorta.

The corkscrew aorta is a variant of the normal anatomical course of the aorta. This rare condition is characterized by a marked tortuosity of the aorta. In our experience it concerns the tract of subrenal aorta, that is an unusual condition, since there are no other cases in the literature. It is characterized by the presence of at least two kinking, and a coiling interposed among them. It is diagnosed by Angio-CT and its response is incidental, being from an asymptomatic clinical point of view.

The anti-proliferative effects of adiponectin on human lung adenocarcinoma A549 cells and oxidative stress involvement.

Adiponectin (Acrp30) plays an important role in energy metabolism and inflammation. Recently, in vivo serum Acrp30 levels have been reported to be correlated to risk of developing several types of cancers such as lung cancer, and in vitro studies have demonstrated a role for Acrp30 in the control of cell proliferation and survival. However, the molecular effects of Acrp30 on lung cancer have not yet been clearly defined. In the present study, we investigated the effects of different concentrations of Acrp30 on the A549 human alveolar epithelial cell line, an in vitro model of lung adenocarcinoma. A549 cells were exposed to various concentrations of Acrp30 and successively, proliferation, apoptosis and oxidative stress were evaluated by MTT test, caspase activity assay, flow-cytometry and western blotting analysis. Our results demonstrated that Acrp30 causes, in a time- and dose-dependent manner, a reduction of cell viability and duplication together with an increase in cell apoptosis rate. In addition, we found that Acrp30 induces an increase of lipid peroxidation evaluated by TBARS assay and a concomitant reduction of nitric oxide release, both markers of cellular oxidative stress. Taken together, our data on A549 cells provides new insight into potential involvement of Acrp30 on physio-pathologic mechanisms of lung diseases through interference with proliferation, apoptosis and oxidative status.

Analysis of hypoxia-associated dendritic cells in colitic mice and effects of probiotics on IL-10 production in inflammatory dendritic-cells under hypoxia.

The aim of this study was to analyse hypoxia-associated dendritic cells (DCs) in colitic mice and the effects of probiotics on interleukin (IL)-10 production in inflammatory DCs under hypoxic conditions. Extensive hypoxia was observed in the colonic mucosa of dextran sodium sulphate-induced colitic mice. Flow cytometric analysis demonstrated that hypoxia-inducible factor-1α+ DCs in colonic lamina propria (CLP) lymphocytes and mesenteric lymph nodes (MLN) were more abundant in colitic mice than those in controls. Among three subsets of DCs, i.e. plasmacytoid DCs, conventional DCs (cDCs), and monocyte-derived DCs (mDCs), cDCs and mDCs were more abundant in CLP of colitic mice. Bone marrow-derived Flt-3L-induced DCs (Flt-DCs) but not bone marrow-derived GM-CSF-induced DCs (GM-DCs), incubated with 1% O2 exhibited an inflammatory phenotype, with higher CD86, IL-6, and tumour necrosis factor-α expression, and lower IL-10 levels than those in Flt-DCs incubated with 21% O2. The hypoxia-induced decrease in IL-10 expression in Flt-DCs was restored by Bifidobacterium bifidum JCM 1255T promoted IL-10 expression through the p38 pathway under normoxic conditions. The anti-inflammatory effects of B. bifidum JCM 1255T in Flt-DCs were mediated through different cellular mechanisms under hypoxic and normoxic conditions. B. bifidum JCM 1255T could be used therapeutically for its anti-inflammatory effects.

Raw BIA variables are predictors of muscle strength in patients with chronic obstructive pulmonary disease.

BACKGROUND/OBJECTIVES: Although loss of fat-free mass (FFM) and reduced muscle strength are highly prevalent in chronic obstructive pulmonary disease (COPD), only few data are available on the relationships of handgrip strength (HGS) and respiratory muscle strength with body composition in such disease. In particular, we aimed to assess whether raw bioelectrical impedance (BIA) variables were independent predictors of muscle strength in COPD patients, possibly more significant than anthropometric variables and BIA-based estimates of FFM. SUBJECTS/METHODS: Two hundred and thirty-seven COPD patients (161 males and 76 females) underwent respiratory, anthropometric, BIA, HGS and respiratory muscle strength (maximum inspiratory or expiratory pressure=MIP and MEP) measurements. Bioimpedance index (BI index=height square/whole-body impedance) and phase angle (PhA) were considered as raw BIA variables. FFM was estimated using three disease-specific BIA equations. RESULTS: In COPD patients a stronger correlation was observed between HGS and PhA compared to the ones with anthropometric variables or FFM estimates. Multiple regression analysis showed that combining BI index and PhA (plus age in male patients) accounted for 50.2% and 42.6% of the variance in HGS in male and female patients, respectively. Similarly, BI index and PhA emerged as predictors of both MIP and MEP in males, while in females MIP was related only to PhA and MEP only to BI index. CONCLUSIONS: Raw BIA variables are independent and valuable predictors of HGS and respiratory muscle strength in COPD patients. BI index and PhA could provide useful information for evaluating body composition and better assessing muscle strength and physical fitness in COPD.

Differentially expressed and activated proteins associated with non small cell lung cancer tissues.

BACKGROUND: Lung cancer is a leading cause of mortality. The most common cancer subtype, non small cell lung cancer (NSCLC), accounts for 85-90% all cases and is mainly caused by environmental and genetic factors. Mechanisms involved in lung carcinogenesis include deregulation of several kinases and molecular pathways affecting cell proliferation, apoptosis and differentiation. Despite advances in lung cancer detection, diagnosis and staging, survival rate still remains poor and novel biomarkers for both diagnosis and therapy need to be identified. In the present study, we have explored the potential of novel specific biomarkers in the diagnosis of NSCLC, and the over-expression/activation of several kinases involved in disease development and progression. METHOD: Lung tumor tissue specimens and adjacent cancer-free tissues from 8 NSCLC patients undergoing surgery were collected. The differential activation status of ERK1/2, AKT and IKBα/NF-κß was analyzed. Subsequently, protein expression profile of NSCLC vs normal surrounding tissue was compared by a proteomic approach using LC-MS MS. Subsequently, MS/MS outputs were analyzed by the Protein Discoverer platform for label-free quantitation analysis. Finally, results were confirmed by western blotting analysis. RESULTS: This study confirms the involvement of ERK1/2, AKT, IKBα and NF-κß proteins in NSCLC demonstrating a significant over-activation of all tested proteins. Furthermore, we found significant differential expression of 20 proteins (Rsc ≥ 1.50 or ≤ -1.50) of which 7 are under-expressed and 13 over-expressed in NSCLC lung tissues. Finally, we validated, by western blotting, the two most under-expressed NSCLC tissue proteins, carbonic anhydrase I and II isoforms. CONCLUSION: Our data further support the possibility of developing both diagnostic tests and innovative targeted therapy in NSCLC. In addition to selective inhibitors of ERK1/2, AKT, IKBα and NF-κß, as therapeutic options, our data, for the first time, indicates carbonic anhydrase I and II as attractive targets for development of diagnostic tools enabling selection of patients for a more specific therapy in NSCLC.

Spray-by-spray in situ cross-linking alginate hydrogels delivering a tea tree oil microemulsion.

In this paper we propose an in situ forming ionically cross-linked alginate (Alg) hydrogel delivering a Tea Tree Oil microemulsion (MeTTO) and potentially useful as an advanced dressing for infected wounds. Alg hydrogels were prepared by a spray-by-spray deposition method with the aim to minimize the discomforts during application. From pseudoternary phase diagrams, it was found that proper combination of TTO, water, polysorbate 80 and ethanol gave stable spherical MeTTO with good antimicrobial activity. On this basis, MeTTO at 20% TTO was selected for further inclusion in an Alg hydrogel prepared by alternating sprays of Alg/MeTTO and calcium chloride solutions. Homogeneous dispersion of MeTTO inside cross-linked Alg was assessed by different macroscopic and microscopic methods demonstrating the superior propensity of MeTTO to be integrated in the water-based hydrogel as compared to TTO. Antimicrobial effect of Alg/MeTTO hydrogels on Escherichia Coli strains was remarkable, highlighting the potential of the system as bioactive wound dressing.

Severe obesity prevalence in 8- to 9-year-old Italian children: a large population-based study.

BACKGROUND AND OBJECTIVES: Little information is available on severe obesity in childhood. This study estimates the prevalence of severe obesity in 8- to 9-year-old children resident in Italy and its association with gender, age, geographical area and parents' nutritional status and education using the World Health Organization (WHO) and International Obesity Task Force (IOTF) criteria. SUBJECTS/METHODS: A nationally representative sample of grade 3 Italian students was measured in 2010 (N=42,431) using standardized instruments and methodology. Severe obesity in children was assessed using definitions provided by the WHO and by the IOTF. Prevalence was estimated within categories of sociodemographic variables and their independent effects were estimated using multivariate logistic regression. RESULTS: The estimated prevalence of severe obesity in 2010 was 4.5% (95% confidence interval (CI): 4.2-4.7) according to the WHO definition and 2.7% (95% CI: 2.5-2.9) with IOTF cutoffs. These values were slightly lower than those observed in 2008. The prevalence was higher in males, in 8-year-old children and in the South. Parental low education and high body mass index were strongly associated with childhood severe obesity. CONCLUSION: According to the definition used, between 30,000 and 50,000 children aged 8-9 years suffer severe obesity in Italy.

Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. METHODS: 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. RESULTS: Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. CONCLUSIONS: Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov.

Morphology changes in human lung epithelial cells after exposure to diesel exhaust micron sub particles (PM1.0) and pollen allergens.

In the recent literature there has been an increased interest in the effects of particulate matter on the respiratory tract. The objective of this study was to use an in vitro model of type II lung epithelium (A549) to evaluate the cell ability to take up sub-micron PM(1.0) particles (PM(1.0)), Parietaria officinalis (ALL), and PM(1.0) + ALL together. Morphological analysis performed by Transmission Electron Microscope (TEM) showed that PM and ALL interacted with the cell surface, then penetrating into the cytoplasm. Each single treatment was able to point out a specific change in the morphology. The cells treated appear healthy and not apoptotic. The main effect was the increase of: multilamellar bodies, lysosomal enzymes, microvilli, and presence of vesicle/vacuoles containing particles. These observations demonstrate morphological and functional alterations related to the PM(1.0) and P. officinalis and confirm the induction of the inflammatory response in lung cells exposed to the inhalable particles.

Inflammatory effects on human lung epithelial cells after exposure to diesel exhaust micron sub particles (PM1.0) and pollen allergens.

Asthma is currently defined as a chronic inflammatory disease of the airway. Several evidence indicate that vehicle emissions in cities is correlated with the allergic respiratory diseases. In the present study, we evaluated in the A549 cells the production and release of IL-4, IL-5 and IL-13 after treatment with sub-micron PM(1.0) particles (PM(1.0)), Parietaria officinalis (ALL), and PM(1.0) + ALL together. Our data demonstrated that PM(1.0) + ALL together exhibited the greatest capacity to induce A549 cells to enhance the expression of IL-4 and IL-5 compared with the only PM(1.0) or ALL treatment. Interestingly, IL-13 that is necessary for allergen-induced airway hyper responsiveness, is increased in cells treated with PM(1.0) + ALL together, but is higher expressed when the cells are treated only with the allergen. Our data support the hypothesis that the urban environment damage the acinar lung units and activates cells of the immune system.

Immunomodulatory effects of Lactobacillus casei administration in a mouse model of gliadin-sensitive enteropathy.

Coeliac disease (CD) is a very common food-sensitive enteropathy, which is triggered by gluten ingestion and is mediated by CD4(+) T cells. In addition, alterations in the intestinal microbiota that is normally involved in the homeostasis of GALT (gut-associated lymphoid tissue) seem to play a role in CD. In accordance with these findings, we previously reported that Lactobacillus casei can induce a strong enhancement of the T cell-mediated response to gliadin without inducing enteropathy. In this study, we analysed the effects of L. casei administration in a mouse model of gliadin-induced villous damage that was recently developed and involves the inhibition of cyclo-oxygenase (COX) activities in gliadin-sensitized HLA-DQ8 transgenic mice. To address the issue, we assessed the weight loss, the intestinal cytokine pattern, the density of CD25(+) cells and morphometry of the gut mucosa. We confirmed that COX inhibition in sensitized mice caused villus blunting, dysregulated expression of tumour necrosis factor (TNF)-α and reduced gliadin-specific IL-2 production. Notably, the administration of probiotic strain induced a complete recovery of villus blunting. This finding was associated with a delay in weight decrease and a recovery of basal TNF-α levels, whereas the numbers of CD25(+) cells and the levels of IL-2 remained unchanged. In conclusion, our data suggest that the administration of L. casei can be effective in rescuing the normal mucosal architecture and GALT homeostasis in a mouse model of gliadin-induced enteropathy.

Water buffalo mozzarella cheese stored in polysaccharide-based gels: correlation between prolongation of the shelf-life and physicochemical parameters.

An innovative packaging system has been developed, based on natural gels, that has shown the peculiar characteristic to strongly increase the shelf life of water buffalo Mozzarella cheese. To explain the mechanism of action of the gel, measurements of Ca and Na in the cheese and in the storage liquid were carried out, together with pH determination. A correlation has been found between the constant level of Ca and pH in the cheese and the prolongation of nutritional characteristics; in fact, both parameters diminish significantly in the absence of gel. At the same time, the weight of the cheese in gel remained constant for as long as 30 d. Confocal laser microscopy gave direct evidence of the persistent physical structure of proteins and lipids of Mozzarella when stored in gel.

Gemcitabine, ifosfamide and paclitaxel in advanced/metastatic non-small cell lung cancer patients: a phase II study.

UNLABELLED: Although platinum-based two-drug combinations represent the elective therapeutic approach for advanced/metastatic NSCLC, there is still interest in exploring the efficacy and tolerability of platinum-free combinations including third generation agents in selected NSCLC population. Based on the satisfying activity of gemcitabine (G), ifosfamide (I) and paclitaxel (T) as single agents in NSCLC, we have designed a phase II study to explore an alternative approach to platinum-containing regimens using a combination of these three drugs. To investigate the activity/toxicity of T 175 mg/m2 on day 1, I 3 g/m2 on day 1 (with Mesna uroprotection) and G 1,000 mg/m2 on day 1-8, every 3 weeks in the treatment of advanced/metastatic NSCLC, 46 patients (38 male, 8 female) with NSCLC were enrolled: mean age 58 (range 33-70); Stage IIIB/IV=15/31; ECOG PS 0-1/2=31/15; HISTOLOGY: adenocarcinoma=20, squamous=14, large cell=3, NSCLC=8, adenosquamous=1. A total of 221 cycles have been administered (median number 4.8 for patients). In intent-to-treat analysis, partial response was achieved in 17 patients (36.95%), stable disease and progressive disease was detected in 16 (34.78%) and 10 (21.73%) patients, respectively. Time to progression was 30.9 weeks; median survival time was 42.7 weeks; the survival rates at 12 and 18 months were 34.79 and 15.21%, respectively. No toxic deaths occurred. No patients experienced grade 4 neutropenia and thrombocytopenia. Neutropenia grade 3 occurred in 10 patients (21.7%); Anemia grade 3 in 1 (2.1%); Thrombocytopenia grade 2 in two patients (4.3%) and grade 3 in one (2.1%). Peripheral neuropathy grade 1 occurred in ten (21.7%) and grade 2 in two patients (4.3%). Additional non-haematological toxicities were mild nausea, emesis and fatigue. GIT is well tolerated and active regimen in both advanced and metastatic NSCLC. These data suggest future investigations for GIT schedule as a possible alternative to platinum-based regimens in selected advanced/metastatic NSCLC patients where survival, tolerability and quality of life are the primary goals.

The usefulness of transesophageal echocardiography in the staging of locally advanced lung cancer.

BACKGROUND: The pre-operative staging of locally advanced non-small cell lung cancer (NSCLC) is an important clinical and radiological issue. Computed tomography (CT) scan cannot always provide sufficient information about resectability and some patients may undergo unnecessary thoracotomy. The purpose of this study was to evaluate the utility of transesophageal echocardiography (TEE) in distinguishing T3 from T4 lesions in patients with lung cancer possibly involving cardiovascular structures and to compare its findings with those of computed tomography and, whenever possible, of surgical samples. METHODS: Between January 1998 and December 2001, sixteen patients were referred to our pulmonology unit for evaluation of locally advanced NSCLC possibly involving the heart or great vessels. All patients underwent mediastinal staging with both contrast enhancement CT scan and TEE. RESULTS: The mediastinal staging by CT scan classified eleven patients as T4N0M0 and five patients as T3N0M0. TEE suggested mediastinal extension of the tumour in nine out of sixteen patients, who were eventually classified as T4; the remaining seven patients had no mediastinal involvement according to TEE and were therefore classified as T3. The pathologic staging confirmed clinical TEE staging in all of the ten patients who subsequently underwent surgery. The remaining six patients were excluded from surgery either because of major coexistent illnesses or because refused to be operated on. CONCLUSION: TEE is a useful diagnostic tool in the staging of patients with locally advanced NSCLC which suspect involvement of heart and/or great vessels.

Effects of diesel exhaust particles on human lung epithelial cells: an in vitro study.

Atmospheric particulate matter (PM), an ingredient of urban pollution matter, is a mixture of solid and liquid particles differing in origin, dimension and composition. There is big concern about inhaled PM in urban areas, especially due to its adverse effects on the respiratory system. Diesel exhaust particulate (DEP), which constitutes the major part of PM, is characterized by a carbonic mixture composed of approximately 18,000 different high-molecular-weight organic compounds. Diesel engines release 10 times the amount of NO(2) aldehydes and breathable PM compared to unleaded gasoline engines and more than 100 times that produced by catalysed gasoline engines; these data gain great significance when taken into account the fact that diesel-powered vehicles are becoming more and more popular. DEP polyaromatic hydrocarbons (PAH), once deposited on airways mucous surfaces easily pass through epithelial cells (ECs) membranes, bind themselves to cytosolic receptors and then affect cell growth and differentiation. Human lung epithelial cells and macrophages engulf DEP, this resulting in increased proinflammatory cytokines release (IL-6, IL-8 and GM-CSF). We investigated the biological effects of DEP-PM on the human lung EC line A549. Light microscopy analysis suggested the presence of cell wall alterations, and provided evidence of PM internalization and cytoplasmic vacuolization. Following PM stimulation, nuclei also were seen undergo clear gross morphological modifications. Immunocytochemistry was used to detect intracytoplasmic IL-6 and IL-8 expression.

Phase II trial of temozolomide in children with recurrent high-grade glioma.

PURPOSE: The objective of the study was to evaluate the efficacy and toxicity of Temozolomide (TMZ) administered for 5 consecutive days in three daily dosing in children with recurrent or refractory high-grade glioma. PATIENTS AND METHODS: Twenty-four patients with a median age of 10.5 years were enrolled onto this open-label, multicenter, phase II study. The patients were previously treated with surgical resection (17 of 24), radiotherapy (19 of 24) and chemotherapy (18 of 24). Therapy was administered orally three times a day for 5 consecutive days at the dose of 200 mg/m(2)/dx5 for chemotherapy naive patients. In patients heavily pretreated with chemotherapy the starting dose was of 150 mg/m(2)/dx5. RESULTS: A total of 95 cycles were administered. The median progression free-survival (PFS) was 3 months for the entire group while disease stabilization was obtained in 7 patients (29.1%), all with supratentorial tumors. No CR or PR was observed. TMZ treatment showed a limited toxicity. Thrombocytopenia was the most common hematological adverse effect. Our data suggest a marginal activity of TMZ in children with recurrent high-grade glioma.