Statin use and survival in resectable pancreatic cancer: confounders and mechanisms.

A first point regards the possible activity of drugs other than statins, such as aspirin or metformin, against pancreatic cancer. As many patients use a combination of these drugs, one might speculate that the association between simvastatin and overall survival in resected pancreatic cancer patients might also be explained by the concomitant use of aspirin or metformin, or that these drugs might result synergistic, as hypothesized for colorectal cancer (3). We wonder whether the authors had access to data on aspirin or metformin use for their population. A second point regards the very high 45% rate of simvastatin or lovastatin users reported by the authors. This figure is different from that of many European countries, thus possibly limiting the attributable fraction of cases for whom the observed findings can be replicated

Rascacielos a la italiana. Construcción de gran altura en los años cincuenta y sesenta

In the fifties and sixties, while Italian engineering was receiving important international awards, the theme of the tall building attracted the attention of the best architects. They made it a field of design experimentation, immediately sensing how the strategic use of the structure could revolutionize the already stereotyped image of the all-steel and glass towers proposed by the International Style. Gio Ponti, Luigi Moretti and the BBPR thus created formidable partnerships with Pier Luigi Nervi and Arturo Danusso, the most active engineers in the field of skyscraper design. The result was at least three masterpieces, among the works created in those years: the Velasca tower and the Pirelli skyscraper in Milan and the Stock Exchange tower in Montreal, which, at the time of its completion, also marked the record for the highest reinforced concrete building in the world.En los años cincuenta y sesenta del siglo XX, mientras la ingeniería italiana recibía importantes premios internacionales, el diseño de los edificios en altura atraía la atención de los mejores arquitectos. Estos entendieron inmediatamente lo mucho que el empleo estratégico de la estructura habría podido revolucionar la ya de por sí estereotipada imagen de la torre de acero y vidrio propuesta por el Estilo Internacional, y lo convirtieron en un campo de experimentación. De esta forma Gio Ponti, Luigi Moretti y la BBPR desarrollaron extraordinarias colaboraciones con Pier Luigi Nervi y Arturo Danusso, los ingenieros más activos en el campo del diseño de rascacielos. De entre los proyectos realizados en esos años, este proceso de colaboración dió como resultado a al menos tres obras maestras: la torre Velasca, el rascacielos Pirelli y la torre de la Bolsa de Valores de Montreal. Esta última, en el momento de su finalización, además significó el récord del edificio de hormigón armado más alto del mundo

The use of complementary and alternative medicine is frequent in patients with pancreatic disorder

BACKGROUND: Herbal remedies and other complementary and alternative medicine (CAM) are used by 30% of the patients with liver and inflammatory bowel diseases. However, there are no data regarding CAM use in patients with pancreatic disorders, including potential pancreatotoxicity. AIM OF THE STUDY: The aim of the study was to assess the prevalence of CAM use in patients with pancreatic disorders and screen for pancreatotoxicity. MATERIALS AND METHODS: This was a cross-sectional survey of consecutive outpatients seen at a Pancreas Center. Data were collected in a specific questionnaire. Descriptive statistics were used to analyze the prevalence and the patterns of CAM use. Characteristics associated with CAM use were analyzed by appropriate statistics. RESULTS: Of 108 patients (52% male; mean age, 65±13 years), 47 (43.5%) used CAM. The use of CAM was more frequent among patients with previous acute pancreatitis (47%). Reported reasons for the use of CAM were to help standard therapies and for an overall better feeling. About 61% of the patients reported advantages with treatment. As compared with nonusers, CAM users were more often female (55% vs. 42%), with a higher school degree (43% vs. 36%), more frequently performing physical activity (51% vs. 41%), and reporting anxiety (45% vs. 31%). However, none of these differences were statistically significant. Three patients with previous acute pancreatitis reported the use of Serenoa repens that is potentially pancreatotoxic. DISCUSSION: The rate of CAM use in patients with pancreatic disorders is similar to those reported for other digestive diseases. CAM use seems to be more frequent in women with a higher education level and a "healthier lifestyle." Patients might not be aware of the potential pancreatotoxicity of CAM, which should be carefully considered by physician

Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first-line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of this disease. We found that chronic exposure of PDAC cells to gemcitabine selected a subpopulation of cells that are drug-resistant (DR-PDAC cells). Importantly, alternative splicing (AS) of the pyruvate kinase gene (PKM) was differentially modulated in DR-PDAC cells, resulting in promotion of the cancer-related PKM2 isoform, whose high expression also correlated with shorter recurrence-free survival in PDAC patients. Switching PKM splicing by antisense oligonucleotides to favor the alternative PKM1 variant rescued sensitivity of DR-PDAC cells to gemcitabine and cisplatin, suggesting that PKM2 expression is required to withstand drug-induced genotoxic stress. Mechanistically, upregulation of the polypyrimidine-tract binding protein (PTBP1), a key modulator of PKM splicing, correlated with PKM2 expression in DR-PDAC cell lines. PTBP1 was recruited more efficiently to PKM pre-mRNA in DR- than in parental PDAC cells. Accordingly, knockdown of PTBP1 in DR-PDAC cells reduced its recruitment to the PKM pre-mRNA, promoted splicing of the PKM1 variant and abolished drug resistance. Thus, chronic exposure to gemcitabine leads to upregulation of PTBP1 and modulation of PKM AS in PDAC cells, conferring resistance to the drug. These findings point to PKM2 and PTBP1 as new potential therapeutic targets to improve response of PDAC to chemotherapy.Oncogene advance online publication, 3 August 2015; doi:10.1038/onc.2015.270

Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

The bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells

The mediterranean diet slows down the progression of aging and helps to prevent the onset of frailty: A narrative review

The aging population is rapidly increasing all over the world. This results in significant implications for the planning and provision of health and social care. Aging is physiologically characterized by a decrease in lean mass, bone mineral density and, to a lesser extent, fat mass. The onset of sarcopenia leads to weakness and a further decrease in physical activity. An insufficient protein intake, which we often observe in patients of advanced age, certainly accelerates the progression of sarcopenia. In addition, many other factors (e.g., insulin resistance, impaired protein digestion and absorption of amino acids) reduce the stimulation of muscle protein synthesis in the elderly, even if the protein intake is adequate. Inadequate intake of foods can also cause micronutrient deficiencies that contribute to the development of frailty. We know that a healthy eating style in middle age predisposes to so-called “healthy and successful” aging, which is the condition of the absence of serious chronic diseases or of an important decline in cognitive or physical functions, or mental health. The Mediterranean diet is recognized to be a “healthy food” dietary pattern; high adherence to this dietary pattern is associated with a lower incidence of chronic diseases and lower physical impairment in old age. The aim of our review was to analyze observational studies (cohort and case–control studies) that investigated the effects of following a healthy diet, and especially the effect of adherence to a Mediterranean diet (MD), on the progression of aging and on onset of frailty

Investigation of a passive control system for limiting cavitation inside turbomachinery under different operating conditions

Abstract Herein, a new passive control system for limiting cavitation inside turbomachinery has been applied to a NACA0009 hydrofoil. The basic idea is to introduce slots nearby its leading edge, connecting pressure and suction sides of the hydrofoil, in order to increase locally the pressure on its suction side and to prevent cavitation from developing. The cavitating flow developed around a two-dimensional hydrofoil is here considered since it is an archetype of cavitation nearby the leading edges of the impeller vanes. Thus, the flow field developed at the leading edge of both the original and modified hydrofoil has been studied at different angles of attack in order to reproduce a wide range of operating conditions that occur inside turbomachinery. Eventually, a comparison of their performance in terms of polars (C L and C D ) and vapour volume fractions (α v ) is performed

Iron deficiency anemia caused by nonspecific (idiopathic) small bowel ulceration: an uncommon presentation of an uncommon disease.

Ulcers of the small bowel are rare, and in most cases are due to infections, inflammatory bowel diseases, malignancies or drugs. When none of these causes is recognized, they are classified as 'nonspecific' or idiopathic. Such lesions are uncommon, and in most cases present with occlusion. A case of a middle-aged woman with iron deficiency anemia due to occult bleeding, with negative gastroscopy and colonoscopy is presented. The diagnosis of a small bowel pathology resembling Crohn's disease was made by small bowel follow through and small intestine contrast ultrasonography. An ileal ulcer was identified at surgery, and after resection the patient experienced a stable recovery from the anemia without ulcer recurrence. Neither histology nor clinical or biochemical features suggested the diagnosis of an inflammatory bowel disease. Other possible causes were unlikely and the lesion was therefore diagnosed as idiopathic. This report also focuses on the need and the modality to investigate the small bowel in iron deficiency anemia patients

The prevalence of pancreatic cystic lesions in patients with liver cirrhosis is double that in controls

Background and aims: Pancreatic cystic lesions (PCLs) are commonly diagnosed incidentally and are often preneoplastic. Their presence may influence the management of patients with chronic diseases such as liver cirrhosis (LC). This study evaluated the prevalence and nature of PCLs in LC patients. Methods: The images of 192 LC patients and 192 controls who underwent either computed tomography scan or nuclear magnetic resonance were reviewed for the presence and nature of PCLs. The prevalence of PCLs in both groups and differences between LC patients with and without PCLs were analysed. Multiple logistic regression analysis was used to investigate factors associated with PCLs. Results: Thirty-five of 192 LC patients (18%) and 19/192 controls (10%) had PCLs (p =.027). The prevalence of presumptive intraductal pancreatic mucinous neoplasm (IPMN) was double in LC patients compared with controls (14% vs 7%; p =.065). In multivariate analysis, age, LC and having undergone a magnetic resonance cholangiopancreatography were factors associated with PCLs and IPMNs. LC patients with PCLs were older at the time of imaging and had a longer history of liver disease (67 vs. 43 months; p = 0.039) compared with LC patients without PCLs. Conclusions: PCLs are more common in LC patients than in controls, and most are IPMNs. The occurrence of PCLs in LC patients seems to be related to age and disease duration