Evidence based medicine and surgical approaches for colon cancer: Evidences, benefits and limitations of the laparoscopic vs open resection

AIM: To report a meta-analysis of the studies that compared the laparoscopic with the open approach for colon cancer resection.

Role of sex hormones in the modulation of cholangiocyte function

Over the last years,cholangiocytes,the cells that line the biliary tree,have been considered an important object of study for their biological properties which involves bile formation,proliferation,injury repair,fibrosis and angiogenesis.Cholangiocyte proliferation occurs in all pathologic conditions of liver injury where it is associated with inflammation and regeneration.During these processes,biliary cells start to secrete different cytokines,growth factors,neuropeptides and hormones which represent potential mechanisms for cross talk with other liver cells.Several studies suggest that hormones,and in particular,sex hormones,play a fundamental role in the modulation of the growth of this compartment in the injured liver which functionally conditions the progression of liver disease.Understanding the mechanisms of action and the intracellular pathways of these compounds on cholangiocyte pathophysiology will provide new potential strategies for the management of chronic liver diseases.The purpose of this review is to summarize the recent findings on the role of sex hormones in cholangiocyte proliferation and biology.

Multiple giant diverticula of the foregut causing upper gastrointestinal obstruction

Small bowel diverticulosis represents an uncommon disorder (except for Meckel diverticulum) often misdiagnosed since it causes non-specific gastroin- testinal symptoms. Most of times the diagnosis is carried out in case of related complications, such as diverticulitis, hemorrhage, perforation or obstruction. Intestinal obstruction can be caused by inflammatory stenosis due to repeated episodes of diverticulitis, volvulus, intussusception or jejunal stones. Herein we report a case of multiple jejunal diverticula causing chronic gastrointestinal obstruction.

Follow-up of endovascular aortic aneurysm repair:Preliminary validation of digital tomosynthesis and contrast enhanced ultrasound in detection of medium- to long-term complications

AIM: To validate the feasibility of digital tomosynthesis of the abdomen(DTA) combined with contrast enhanced ultrasound(CEUS) in assessing complications after endovascular aortic aneurysm repair(EVAR) by using computed tomography angiography(CTA) as the gold standard.METHODS: For this prospective study we enrolled 163 patients(123 men; mean age, 65.7 years) referred for CTA for EVAR follow-up. CTA, DTA and CEUS were performed at 1 and 12 mo in all patients, with a maximum time interval of 2 d.RESULTS: Among 163 patients 33 presented complications at CTA. DTA and CTA correlated for the presence of complications in 32/33(96.96%) patients and for the absence of complications in 127/130(97.69%) patients; the sensitivity, specificity, positive predictive value(PPV), negative predictive value(NPV) and accuracy of DTA were 97%, 98%, 91%, 99%, and 98%, respectively. CEUS and CTA correlated for the presence of complications in 19/33(57.57%) patients and for the absence of complications in 129/130(99.23%) patients; the sensitivity, specificity, PPV, NPV and accuracy of CEUS were 58%, 99%, 95%, 90%, and 91%, respectively. Sensitivity, specificity and accuracy of combining DTA and CEUS together in detecting EVAR complications were 77%, 98% and 95%, respectively.CONCLUSION: Combining DTA and CEUS in EVAR follow-up has the potential to limit the use of CTA only in doubtful cases.

Phylogeny of Culex theileri virus flavivirus in Spain, Myanmar, Portugal and Turkey

Objective: To study the genetic diversity of Culex theileri flavivirus and the spread of this virus among Spain, Portugal and Turkey.Methods: A database consisting of 55 sequences of the NS5/3'UTR region of Culex theileri flavivirus group downloaded from GenBank were aligned and manual edited with Bioedit.ModelT est v.3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data.Maximum likelihood analysis was performed using MEGA7.The phylogenetic signal of the dataset was investigated by the likelihood mapping analysis.Results: The phylogenetic tree showed three clusters.Myanmar sequences clusterd together with Turkish sequences, Spain and Portugal strains grouped together and two Turkish sequences grouped separately.Selective pressure analysis showed a moderate percentage of sites(22.5%) under pervasive negative selection and only 1% under pervasive positive selection.The sites subject to selective pressure in CTFV RdRp NS5 fragments have been located onto the predicted three-dimensional structure.Conclusions: Phylogenetic and evolutionary analysis can be an important tool for understanding the evolutionary impact of the probable contemporary existence between nonpathogenic and pathogenic flaviviruses among these vectors.

Histamine regulation of hyperplastic and neoplastic cell growth in cholangiocytes

Histamine has long been known to be involved in inflammatory events.The discovery of antihistamines dates back to the first half of the 20th century when a Swiss-Italian pharmacologist,Daniel Bovet began his work.In 1957 he was awarded a Nobel Prize for his production of antihistamines for allergy relief.Since that time,histamine has been found to play a role in other events besides allergic reaction.Possiblyun believable to Bovet and his peers,histamine has now been marked as playing a role in liver pathologies including hepatobiliary diseases.

Existing European Buildings and Cities： Economic Improvement and Evaluation of the Cost-Benefit Related to Lifecycle and Performance

In this study, the interdependency is presented between the characteristics of the buildings and the relative economic value, in order to plan economic policies and preconditions for improving the quality of the European buildings heritage through access, by an holistic approach, to the necessary f＇mancial resources. The economic value of a real estate asset is closely connected to the construction features and their performance over time （lifecycle）. Safer, more comfortable and productive buildings for inhabitants are at the same time more operationally efficient and economically convenient for the owners. Solidity characteristics and static resistance to earthquakes, eco-efficiency and other constructive qualities of the building will provide benefits in the long term, and they are directly related the LCC （life cycle cost） including specific construction and/or maintenance costs. Moreover, these characteristics have an impact on the ＂market value＂ and on the ＂mortgage lending value＂ of properties, as well as on the possibility of financing the purchase through access to more affordable mortgages, and to make really feasible conversions even in the absence of public financial resources. This study introduces a new approach for conversions involving whole buildings or city areas. This research identifies the economic sustainability of a project by combining principles and suitable methodologies, together with performance and other characteristics. These aspects constitute the essential prerequisite for obtaining mortgages from banks and/or financial resources from international investors.

Estrogens and the pathophysiology of the biliary tree

The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors （ER-α） and （ER-β） subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades JERK1/2 （extracellular regulated kinases 1/2, PI3-kinase/AKT （phosphatidylinositol-3＇ kinase/AKT）] typical of growth factors such as insulin like growth factor （IGF1）, nerve growth factor （NGF） and vascular endothelial growth factor （VEGF）, thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.

S100B protein in the gut:The evidence for enteroglial-sustained intestinal inflammation

Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system （CNS）. In recent years, the role of enteric glial cells （EGCs） has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the SIOOB protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, SIOOB overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. SlOOB-mediated pro-inflammatory effects are not limited to the brain： SIOOB overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and SIOOB protein occurring in intestinal inflammation deriving from such.

Cholangiocytes and blood supply

The microvascular supply of the biliary tree, the peribiliary plexus （PBP）, stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts （SEMvcc） technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra-and intrahepatic biliary tree. In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a morecomplex vascular network. After common duct ligation （BDL）, progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a three-dimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Considering the enormous extension of the PBP during BDL, the possible role played by the Vascular Endothelial Growth Factor （VEGF） is evaluated. VEGF-A,VEGF-C and their related receptors appeared highly immunopositive in proliferating cholangiocytes of BDL rats. The administration of anti-VEGF-A or anti-VEGF-C antibodies to BDL rats as well as hepatic artery ligation induced a reduced bile duct mass. The administration of rVEGF-A to BDL hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats. These data suggest the role of arterial blood supply of the biliary tree in conditions of cholangiocyte proliferation, such as it occurs during chronic cholestasis. On the other hand,the role played by VEGF as a tool of cross-talk between cholangiocytes and PBP endothelial cells suggests that manipulation of VEGF release and function could represent a therapeutic strategy for human pathological conditions characterized by damage of hepatic artery or the biliary tree.

Dynamic and reversibility of heterochromatic gene silencing in human dis-ease

In eukaryotic organisms cellular fate and tissue specific gene expression are regulated by the activity of proteins known as transcription factors that by interacting with specific DNA sequences direct the activation or repression of target genes. The post genomic era has shown that transcription factors are not the unique key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, post-translational modifications of histone proteins, remodeling of nucleosomes and expression of small regulatory RNAs also contribute to regulation of gene expression, determination of cell and tissue specificity and assurance of inheritance of gene expression levels. The relevant contri- bution of epigenetic mechanisms to a proper cellular function is highlighted by the effects of their deregulation that cooperate with genetic alterations to the development of various diseases and to the establishment and progression of tumors.

Sustained virological response: A milestone in the treatment of chronic hepatitis C

AIM: To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response. METHODS: One hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico Ⅱ". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis. RESULTS: The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis. CONCLUSION: Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that viruseradication following interferon treatment can last up to 20 years.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.

An unusual case of fatty liver in a patient with desmoid tumor

A desmoid tumor,also known as aggressive fibromatosis,is a rare benign neoplasm that arises from fascial or musculoaponeurotic tissues.It can occur in any anatomical location,most commonly the abdominal wall,shoulder girdle and retroperitoneum.The typical clinical presentation is a painless mass with a slow and progressive invasion of contiguous structures.It is associated with a high local recurrence rate after resection.Many issues regarding the optimal treatment of desmoid tumors remain controversial.Aggressive surgical resection with a wide margin(2-3 cm) remains the gold standard treatment with regard to preserving quality of life.Radiotherapy alone has been shown to be effective for the control of unresectable or recurrent lesions.Desmoid tumors tend to be locally infiltrative,therefore,the fields must be generous to prevent marginal recurrence.The radiation dose appropriate for treating desmoid tumors remains controversial.We present a 25-year-old Caucasian man with local recurrence of a desmoid tumor after repeated surgical resection,treated with radiotherapy.The patient achieved complete tumor regression at 4 mo after radiotherapy,and he is clinically free of disease at 12 mo after the end of treatment,with an acceptable quality of life.The patient developed short bowel syndrome as a complication of second surgical resection.Consequently,radiotherapy might have worsened an already present malabsorption and so led to steatohepatitis.

Ketoprofen,peginterferon 2a and ribavirin for genotype 1 chronic hepatitis C:A phaseⅡ study

AIM:To evaluate the safety of adding ketoprofen to pegylated-interferon(PEG-IFN)with or without ribavirin and the effect on viral kinetics,STAT1 activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS)in genotype 1 chronic hepatitis C in a phaseⅡstudy. METHODS:Forty-five patients were studied:fifteen were randomized to PEG-IFN plus ribavirin(PR),16 to PEGIFN plus ketoprofen and 14 to PR and ketoprofen.Themolecular study of IFN-dependent signal transduction was conducted in 9 patients from each group. RESULTS:The combination of ketoprofen and PEG- IFN with or without ribavirin was safe and well tolerated.An early activation of STAT1 was observed in ke-toprofen-treated patients,but this activation was less sustained over time.Conversely,ketoprofen plus PEG- IFN and ribavirin induced an early and sustained increase of 2'-5'OAS transcription starting 24 h after the first dose until the 36th wk.These data are consistent with the clinical results,showing a better sustained virological response and a lower relapse rate in patients receiving ketoprofen plus PEG-IFN and ribavirin. CONCLUSION:The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies.

The Problems of the Safety Evaluation of Biotechnology Derived Drugs

Recent years have witnessed rapid advances in the toxicologic assessment of biotechproducts.Safety assessment of a biotech product is a complex and multiple process.This includes a knowledge of its pharmaco-biological characteristics,and identifyingthe target patient population and the proposed clinical application. To make a decision on the safe human application(the products are administering tohumans for therapeutic purposes),besides the identity and purity of the final product,

Human papillomavirus does not have a causal role in colorectal carcinogenesis

AIM: To investigate the presence of human papillomavirus(HPV) DNA along with the integration,the quantification and the expression of the HPV16 in colorectal cancers.METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA.The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples.The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios.HPV16-positive tumors were also evaluated for(1) E2,E4,E5,E6 and E7 viral gene ng quantification;(2) relative quantification compared to W12 cells; and(3) viral E2,E4,E5,E6 and E7 mR NA transcripts by real-time polymerase chain reaction.RESULTS: HPV infection was detected in 16.9% of all tumors examined,and HPV16 was the most frequent type detected(63.6% of positive tissues).Notably,the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers(χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns).HPV16 DNA was present exclusively in episomal form,and the HPV16 E2,E4,E5,E6 and E7 genes were detected in tracenanogram quantities.Furthermore,the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage.Although the extractions were validated by housekeeping gene expression,all the HPV16 positive tissues were transcriptionally inactive for the E2,E4,E5,E6 and E7 mR NAs.CONCLUSION: Based on our results,HPV is unlikely involved in colorectal carcinogenesis.

Fuzzy-entropy based robust optimization criteria for tuned mass dampers

Tuned mass dampers (TMD) are well known as one of the most widely adopted devices in vibration control passive strategies. In the past few decades,many methods have been developed to find the optimal parameters of a TMD installed on a structure and subjected to a random base excitation process,but most of them are usually based on an implicit assumption that all of the structural parameters are deterministic. However,in many real cases this simplification is unacceptable,so robust optimal design criteria becomes aviable alternative to better support engineers in the design process. In Robust Design Optimization (RDO) approaches,indeed the solution must be able to not only minimize the performance but also to limitits variation induced by uncertainty. Most of the currently available RDO methods are based on a probabilistic description of the model uncertainty,even if in many cases they are not able to explicitly include the influence of all the possible sources of uncertainties. Therefore,in this study,a fuzzy version of the robust TMD design optimization problem is proposed. The consistency of the fuzzy approach is studied with respect to the available non-probabilistic formulations reported in the literature and an application to an example of a robust design of a linear TMD subjected to base random vibrations in the presence of fuzzy uncertainties. The results show that the proposed fuzzy-based approach is able to give a set of optimal solutions both in terms of structural efficiency and sensitivity to mechanical and environmental uncertainties.

Does Intellectual Capital Affect Business Performance？

The aim of this paper is to assess the impact of intellectual capital （IC） on firms＇ financial performance with reference to a sample of companies operating in the European Union （EU） area during the period from 2006 to 2013. The analyses are further differentiated by country of domicile, industry sector, and historical period （pre-crisis and crisis）. We investigate whether the value of the components of IC is a relevant factor that influences firms＇ performance, proposing and testing a modified version of the value added intellectual capital （VAICTM） model which also considers country-specific differences in terms of default risk. The empirical results evidence the relevance of the information on IC disclosed by companies. Differences arise depending on the reference country, industry, and historical period examined. The main limitations of the research are the unbalanced structure of the sample among countries and industries and the specificity of the examined sample （listed firms applying IAS/IFRS system）. The main implication of the study is that, since we demonstrate the value relevance of IC, our findings could be of interest for standard setters for defining a standard （qualitative and quantitative） level of information on human resources to be disclosed by companies in their financial statements. Our contribution to the literature is the proposal of some relevant modifications to the original VAICTM model and providing new evidence on the influence that IC had in recent years on business performance in the EU.

乳腺MRI检查预测粗针活检为交界性病变的恶性可能性的价值:前瞻性评估

目的前瞻性研究对于粗针活检为交界性病变应用乳腺MRI预测其恶性的价值。材料与方法本前瞻性研究获得地区伦理委员会批准,所有病人均签署了知情同意书。