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.METHODS:Forty-seven manuscripts were reviewed,33 of which employed for meta-analysis according to the PRISMA guidelines.The results were differentiated according to the study design(prospective randomized trials vs case-control series)and according to the tu-mor’s location.Outcome measures included:(1)shortterm results(operating times,blood losses,bowel function recovery,post-operative pain,return to the oral intake,complications and hospital stay);(2)oncological adequateness(number of nodes harvested in the surgical specimens);and(3)long-term results(including the survivals’rates and incidence of incisional hernias)and(4)costs.RESULTS:Meta-analysis of trials provided evidences in support of the laparoscopic procedures for a several short-term outcomes including:a lower blood loss,an earlier recovery of the bowel function,an earlier return to the oral intake,a shorter hospital stay and a lower morbidity rate.Opposite the operating time has been confirmed shorter in open surgery.The same trend has been reported investigating case-control series and cancer by sites,even though there are some concerns regarding the power of the studies in this latter field due to the small number of trials and the small sample of patients enrolled.The two approaches were comparable regarding the mean number of nodes harvested and long-term results,even though these variables were documented reviewing the literature but were not computable for meta-analysis.The analysis of the costs documented lower costs for the open surgery,however just few studies investigated the incidence of postoperative hernias.CONCLUSION:Laparoscopy is superior for the majority of short-term results.Future studies should better differentiate these approaches on the basis of tumors’location and the post-operative hernias.

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.

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.

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.

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.

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 S100B protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, S100B 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. S100B-mediated pro-inflammatory effects are not limited to the brain: S100B 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 S100B protein occurring in intestinal inflammation deriving from such.

Cholangiocytes and blood supply

胆汁的树的微脉管的供应，仙子胆管丛(PBP ) ，源自肝的动脉树枝和流动进肝窦状隙。PBP 的详细三维的研究被使用扫描电子执行了显微镜学脉管的腐蚀演员组(SEMvcc ) 技术。认为 PBP 在支持胆汁的上皮的能分泌、吸收性的功能起一个基本作用，他们在常态和病理的组织被探索。正常的肝证明 PBP 安排在 extra-附近 -- 并且肝内的胆汁的树。在小门道， PBP 被日益增多地继续了它显示出一个更复杂的脉管的网络的额外的肝的 PBP 的 capillaries 的单个层描绘。在普通的管结扎(BDL ) 以后，胆汁管和 PBP 增长的进步修正被观察。PBP 介绍在许多胆汁管附近安排的一个三维的网络并且作为容器的捆出现，由有典型圆网孔结构的同类的直径的 capillaries 镇静。PBP 网络从显得正常的正弦曲线网络是容易可区分的。在 BDL 期间考虑 PBP 的庞大的延期，脉管的内皮生长因素(VEGF ) 起的可能的作用被评估。VEGF -- A， VEGF-C 和他们的相关受体高度出现了在 BDL 老鼠的增殖的 cholangiocytes 积极的免疫。到象肝的动脉结扎一样的 BDL 老鼠的 anti-VEGF-A 或 anti-VEGF-C 抗体的管理导致了一个减少的胆汁管团。rVEGF 的管理 -- 到 BDL 肝的动脉的 A 绑扎老鼠阻止了 cholangiocyte 增长和 VEGF 的减少 -- 表情作为与 BDL 控制老鼠相比。这些数据处于 cholangiocyte 增长的条件建议胆汁的树的动脉的血供给的角色，例如它发生在长期的胆汁郁积期间。在另一方面， VEGF 作为在 cholangiocytes 和 PBP endothelial 之间的串音的一个工具起的作用建议 VEGF 版本和功能的那操作能为肝的动脉或胆汁的树的损坏描绘的人的病理学的条件代表治疗学的策略。

Estrogens and the pathophysiology of the biliary tree

有关不同纸巾上的雌激素效果的科学框架在最后十年期间极其膨胀了，当时雌激素受体(嗯) 子类型被识别。雌激素是不仅必要的因为雌性生殖系统，而且他们也包括心血管系统，骨头，大脑和肝在另外的纸巾控制基本功能。最近，在他们调制 cholangiocytes 的增生的和分泌活动的地方，雌激素被显示了指向胆汁的树，上皮细胞衬里胆汁管。由在两雌激素受体(ER-alpha ) 并且(上扮演嗯贝它) 子类型，并且由激活 genomic 或 non-genomic 小径，雌激素在生长因素和 cytokines 的复杂的环起一个关键作用，它调制 cholangiocytes 的增生的反应损坏。明确地，雌激素激活细胞内部的发信号的串联[英皇家空军之阶级最低之兵( 1/2 )(细胞外的调整家族 ases ( 1/2 )，PI3- kinase/AKT (phosphatidylinositol-3' kinase/AKT )]典型地代表象象生长因素( IGF1 )一样的胰岛素那样的生长因素，神经生长因素( NGF )和脉管的内皮生长因素( VEGF )，因此加强他们的行动。另外，雌激素在增殖的 cholangiocytes 刺激不同生长因素的分泌物。这评论明确地处理与雌激素处于正常、病理学的条件由调制 cholangiocyte 功能的角色和机制有关的最近的进展。

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.

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.

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.

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.

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。