Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.

Recent advances in multidisciplinary management of hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients' presentations, a multidisciplinaryteam should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.

Significance of serum leptin and adiponectin levels in Egyptian patients with chronic hepatitis C virus associated hepatic steatosis and fibrosis

AIM:To study serum levels of leptin and adiponectin in patients with chronic hepatitis C virus infection genotype-4(HCV-4) related steatosis and fibrosis.METHODS:We prospectively studied 45 untreated men with chronic HCV-4,with proven steatosis(group Ⅰ,30 patients),and fibrosis(group Ⅱ,15 patients),on liver biopsy.In addition,15 healthy men(group Ⅲ),matched for age,and body mass index were included.However,we excluded another five patients with steatohepatitis,and six patients with cirrhosis.We measured total serum leptin and adiponectin levels,as potential predictors for liver steatosis and fibrosis.Also,a correlation between these adipokines and various clinical and laboratory data were evaluated.All subjects were selected from Tropical and Internal medicine departments,Menoufiya University Hospital,Menoufiya,Egypt,during the period from February 2010 to August 2011.RESULTS:In group Ⅰ,severity of hepatic steatosis was mild,moderate,and severe,in 19 patients(63.5%),8 patients(26.5%),and 3 patients(10%),respectively.In contrast,in group Ⅱ,hepatic fibrosis was found to be in stage 1,2,and 3,in 6 patients(40%),in 6 patients(40%),and in 3 patients(20%),respectively.On comparing group Ⅰ with group Ⅱ,there was a significant decrease in serum adiponectin levels(131.4 ± 7.91 pg/mL vs 436 ± 9.75 pg/mL,P < 0.001),while there was no significant difference between both groups regarding serum leptin levels(34.69 ± 7.69 ng/mL vs 35.17 ± 1.06 ng/mL,P > 0.05).However,in the same group,when compared with group Ⅲ,there was a significant increase in serum leptin levels(34.69 ± 7.69 ng/mL vs 10.69 ± 0.84 ng/mL,P < 0.001),while there was a significant decrease in serum adiponectin levels(131.4 ± 7.91 pg/mL vs 342.4 ± 44.48 pg/mL,P < 0.001).In contrast,in group Ⅱ,when compared with group Ⅲ,there was a significant increase in serum leptin and adiponectin levels(35.17 ± 1.06 ng/mL vs 10.69 ± 0.84 ng/mL,P < 0.001,and 436 ± 9.75 pg /mL vs 342.4 ± 44.48 pg/mL,P < 0.05,respectively),while there was no significant difference between both groups regarding serum creatinine(0.83 ± 0.34 vs 0.89 ± 0.24,P > 0.05).On the other hand,serum leptin was not correlated with serum adiponectin in group Ⅰ and in group Ⅱ(r = 0.09,P > 0.05,and r =-0.1,P > 0.05,respectively).However,serum adiponectin was significantly negatively correlated with serum aspartate transaminase in group Ⅰ,but no correlation detected in group Ⅱ(r =-0.39,P > 0.05,and r =-0.03,P > 0.05).CONCLUSION:In male patients with chronic HCV-4,serum adiponectin levels are elevated in hepatic fibrosis,but decreased in steatosis.Therefore,in contrast to leptin,adiponectin may be used as a non-invasive marker.

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

AIM: To assess how ascites and alpha-fetoprotein(AFP) added to the Barcelona Clinic Liver Cancer(BCLC) staging predict hepatocellular carcinoma survival.METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh(CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data(including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed.RESULTS:At the time the data were censored,123/496(24.8%)and 218/564(38.6%)patients with BCLC stages A and B,respectively,had died.Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo[95%confidence interval(95%CI):29.7-32.3]and 22.7mo(95%CI:20.7-24.8),respectively.The presenceof ascites,multiple focal lesions,large tumor size,AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis(P<0.001).Among stage A patients,18%had ascites,33%had AFP≥200 ng/m L,and 8%had both.Their median survival in the presence of ascites was shorter if AFP was≥200 ng/m L(19 mo vs 24 mo),and in the absence of ascites,patients with AFP≥200 ng/m L had a shorter survival(28mo vs 39 mo).For stage B patients,survival for the corresponding groups was 12,18,19 and 22 mo.The one-,two-,and three-year survival rates for stage A patients without ascites and AFP<200 ng/m L were94%,77%,and 71%,respectively,and for patients with ascites and AFP≥200 ng/m L were 83%,24%,and 22%,respectively(P<0.001).Adding ascites and AFP≥200 ng/m L improved the discriminatory ability for predicting prognosis(area under the curve,0.618vs 0.579 for BCLC,P<0.001).CONCLUSION:Adding AFP and ascites to the BCLC staging classification can improve prognosis prediction for early and intermediate stages of hepatocellular carcinoma.

Vibration suppression in multi-tool ultrasonic machining to multi-external and parametric excitations

Ultrasonic machining （USM） is of particular interest for the machining of non-conductive, brittle materials such as engineering ceramics. In this paper, a multi-tool technique is used in USM to reduce the vibration in the tool holder and have reasonable amplitude for the tools. This can be done via dynamic absorbers. The coupling of four nonlinear oscillators of the tool holder and tools representing ultrasonic cutting process are investigated. This leads to a four-degree-of-freedom system subjected to multi-external and multi-parametric excitation forces. The aim of this work is to control the tool holder behavior at simultaneous primary, sub-harmonic and internal resonance condition. Multiple scale perturbation method is used to obtain the solution up to the second order approximations. The different resonance cases are reported and studied numerically. The stability of the system is investigated by using both phase-plane and frequency response techniques. The effects of the different parameters of the tools on the system behavior are studied numerically. Comparison with the available published work is reported.

Small for size syndrome difficult dilemma: Lessons from 10 years single centre experience in living donor liver transplantation

AIM To analyze the incidence, risk factors, prevention, treatment and outcome of small for size syndrome(SFSS) after living donor liver transplantation(LDLT). METHODS Through-out more than 10 years: During the period from April 2003 to the end of 2013, 174 adult-to-adults LDLT(A-ALDLT) had been performed at National Liver Institute, Menoufiya University, Shibin Elkoom, Egypt. We collected the data of those patients to do this cohort study that is a single-institution retrospective analysis of a prospectively collected database analyzing the incidence, risk factors, prevention, treatment and outcome of SFSS in a period started from the end of 2013 to the end of 2015. The median period of follow-up reached 40.50 m, range(0-144 m). RESULTS SFSS was diagnosed in 20(11.5%) of our recipients. While extra-small graft [small for size graft(SFSG)], portal hypertension, steatosis and left lobe graft were significant predictors of SFSS in univariate analysis(P = 0.00, 0.04, 0.03, and 0.00 respectively); graft size was the only independent predictor of SFSS on multivariate analysis(P = 0.03). On the other hand, there was lower incidence of SFSS in patients with SFSG who underwent splenectomy [4/10(40%) SFSS vs 3/7(42.9%) no SFSS] but without statistical significance, However, there was none significant lower incidence of the syndrome in patients with right lobe(RL) graft when drainage of the right anterior and/or posterior liver sectors by middle hepatic vein, V5, V8, and/or right inferior vein was done [4/10(28.6%) SFSS vs 52/152(34.2%) no SFSS]. The 6-mo, 1-, 3-, 5-, 7-and 10-year survival in patients with SFSS were 30%, 30%, 25%, 25%, 25% and 25% respectively, while, the 6-mo, 1-, 3-, 5-, 7-and 10-year survival in patients without SFSS were 70.1%, 65.6%, 61.7%, 61%, 59.7%, and 59.7% respectively, with statistical significant difference(P = 0.00). CONCLUSION SFSG is the independent and main factor for occurrence of SFSS after A-ALDLT leading to poor outcome. However, the management of this catastrophe depends upon its prevention(i.e., selecting graft with proper size, splenectomy to decrease portal venous inflow, and improving hepatic vein outflow by reconstructing large draining veins of the graft).

Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation

Premature ejaculation （PE） is the most common sexual disorder. It affects 20%-30% of adult men; the aetiology of this condition has not yet been elucidated. The aim of this study is to evaluate the efficacy, safety, tolerability, undesirable effects and improved satisfaction with sexual intercourse with tramadol hydrochloride at different dosages for the treatment of PE. A total of 300 patients who presented with lifelong （primary） PE were included in this study. The study was performed for 28 weeks, in which placebo （starch tablet） was given for 4 weeks, and active ingredient （tramadol hydrochloride） was administered at different therapeutic dosages for 24 weeks. Patients were divided into three equal groups, each consisting of 100 patients. The first group （A） was given tramadol hydrochloride capsule 25 mg. The second group （B） was given tramadol hydrochloride capsule 50 mg. The third group （C） was given tramadol hydrochloride capsule 100 mg. All of the 300 participants included completed the study voluntarily. The age of the patients varied from 25 to 50 years. After the treatment period, the recorded data were collected for each group and analysed. The results showed a highly significant increase in the mean intravaginal ejaculatory latency time （IELT） in all groups compared to baseline data （P〈0.0001）. We concluded that using tramadol hydrochloride at different doses on demand for the treatment of PE is effective, safe and tolerable, with minimal undesirable effects, and approval for this indication should be souRht.

Study Bacteriocin Production and Optimization Using New Isolates of <i>Lactobacillus</i>spp. Isolated from Some Dairy Products under Different Culture Conditions

Lactobacilli belong to the group of lactic acid bacteria (LAB), that have several distinguished abilities such as production of lactic acid, enzymes such as β-Galactosidase and natural antimicrobial substances called bacteriocins. Bacteriocin is a biopreservative agent potential of suppressing growth of some contaminant bacteria in food industry but its commercial availability is limited and costly. The study aimed to select isolates of Lactobacillus spp. potential for producing bacteriocins to suppress the growth of Escherichia coli ATCC 25922 and Bacillus subtilis NCIB3610, and to optimize the process of bacteriocin production. Results obtained in this study showed that L. acidophilus isolate CH1 was selected as the best candidate for bacteriocin among the four isolates that tested. The largest amounts of the bacteriocins were synthesized only in MRS medium was supplemented with K2HPO4 (1.0%), Tween 80 (1%), Beef extract (1%), glucose, cyctein and peptone extract (1%). The optimization of culture conditions for bacteriocin production areas showed that corn steep liquor medium was the best medium for all isolates against Bacillus subtilis while no effect was observed on Escherichia coli ATCC 25922 except when used MRS medium. The optimum conditions for bacteriocin production were pH 6.0, temperature 34?C with 4% Phenyl acetamide showing the greatest growth inhibition areas.

Hazardous effects of fried potato chips on the development of retina in albino rats

Objective:To evaluate the hazardous effects of fried potato chips upon the retina of two developmental stages of the albino rats aged 7 and 14 days from parturition.Methods:Pregnant rats were arranged into two groups:control pregnant rats and consequently their delivered newborns until reaching 7 and 14 days old from parturition and fried potato chips group in which pregnant rats at the 6th day of gestation maintained on diet formed of fried potato chips supplied from the market mixed with standard diet at a concentration of 50%per each till 7 and 14 postpartum.Three fold integrated approaches were adopted,namely,histological,ultrastructural and proteomic analysis.Results:Histological examination of the retina of the experimental offsprings revealed many histopathological changes,including massive degeneration,vacuolization and cell loss in the ganglion cell layer,as well as general reduction in retinal size.At the ultrastructural level,the retina of experimental offsprings exhibited number of deformities,including ill differentiated and degenerated nuclear layer,malformed and vacuolated pigment epithelium with vesiculated and fragmented rough endoplasmic reticulum,degenerated outer segment of photoreceptors,as well as swollen choriocapillaris and loss of neuronal cells.Proteomic analysis of retina of the two experimental developmental stages showed variations in the expressed proteins as a result of intoxication which illustrated the adverse toxic effects of fried potato chips upon the retina.Conclusions:It can be concluded that the effect of fried potato chips on the development of retina in rats may be due to the presence of acrylamide or its metabolite.

Ameliorative effect of Morus alba leaves extract against developmental retinopathy in pups of diabetic and aluminum intoxicated pregnant albino rats

Objective: To investigate the possible ameliorative effect of crude water extract of Morus alba(M. alba) leaves on retinopathy of rat pups maternally subjected to diabetes and/or Al intoxication.Methods: Both control and experimental groups were subjected to certain integrated approaches, namely, biochemical assessments, light microscopic investigation, transmission electron microscopic investigation, single cell gel electrophoresis(comet assay) and determination of DNA fragmentation.Results: The retina of pups of diabetic and/or Al-intoxicated mothers exhibited abnormal alterations in retinal cell layers including retinal pigmented epithelium, photoreceptor inner segment and ganglion cells. Increased incidence of DNA fragmentation and apoptosis were evident in pups of diabetic and/or Al-intoxicated mothers. However, retina of pups maternally received M. alba extract plus diabetes or Al-intoxicated alone or in combination showed marked amelioration. Less degree of ameliorations was seen in retina of pups maternally subjected to combined treatment. Furthermore, application of crude water extract of M.alba resulted in amelioration of the alterations of maternal serum glucose as well as Al concentration.Conclusions: Based on the results of the present study, M. alba extract is effective against experimentally diabetic and Al-induced developmental retinopathy.

The role of varicocele sclerotherapy in men with severe ol igo-astheno-teratozoos perm ia

The aim of this study was to verify the role of antegrade scrotal sclerotherapy for the treatment of varicoceles in infertile men with severe oligo-astheno-teratozoospermia （OAT）. The 59 patients with severe OAT in this study underwent antegrade scrotal sclerotherapy for the treatment of varicoceles. The outcome was assessed in terms of improvement in semen parameters and spontaneous conception rate. Semen parameters and reproductive hormones were evaluated before antegrade sclerotherapy （AS） and 6 months after AS. After an average follow-up time of 34.8_＋3.2 months, significant improvement was noted in the mean sperm concentration, motility and morphology in 36 patients （61%）. Spontaneous pregnancy occurred in nine couples （15%）. Six months after treatment, inhibin B levels were significantly higher （P〉0.04）, whereas follicle-stimulating hormone （FSH） levels were significantly lower （P〈0.001） than before treatment. Antegrade internal spermatic vein sclerotherapy can significantly improve seminal parameters and hormonal parameters in men with severe OAT and may even result in spontaneous pregnancy in couples who would otherwise be candidates for intracytoplasmic sperm injection （ICSI）.

Progressive Collapse of Steel Frames

This paper investigates the behavior of steel frames under progressive collapse using the finite element method. Non-linear finite element models have been developed and verified against existing data reported in the literature as well as against tests conducted by the authors. The nonlinear material properties of steel and nonlinear geometry were considered in the finite element models. The validated models were used to perform extensive parametric studies investigating different parameters affecting the behavior of steel frames under progressive collapse. The investigated parameters are comprised of different geometries, different number of stories and different dynamic conditions. The force redistribution and failure modes were evaluated from the finite element analyses, with detailed discussions presented.

How to repair the Hill cipher

The Hill cipher algorithm is one of the symmetric key algorithms that have several advantages in data encryption. However, a main drawback of this algorithm is that it encrypts identical plaintext blocks to identical ciphertext blocks and cannot encrypt images that contain large areas of a single color. Thus, it does not hide all features of the image which reveals patterns in the plaintext. Moreover, it can be easily broken with a known plaintext attack revealing weak security. This paper presents a variant of the Hill cipher that overcomes these disadvantages. The proposed technique adjusts the encryption key to form a dif- ferent key for each block encryption. Visually and computationally, experimental results demonstrate that the proposed variant yields higher security and significantly superior encryption quality compared to the original one.

Experimental Investigation of Progressive Collapse of Steel Frames

This paper reports two new tests conducted to augment available data highlighting the structural performance of multistory steel frames under progressive collapse. The investigated steel frames had different geometries, different boundary conditions, different collapse mechanisms, different damping ratios and different connections. Overall, the paper addresses how multistory frames would behave when subjected to local damage or loss of a main structural carrying element. The obtained results can form a data base for nonlinear finite element models. The deformations of the investigated steel frames and failure modes under progressive collapse were predicted from the finite element analysis, with detailed discussions presented.

Impact of Left Bundle Branch Block on Left Ventricular Mechanics in Patients with Idiopathic Dilated Cardiomyopathy

Objectives: Left bundle branch block (LBBB) is commonly associated with heart failure. We evaluated the prevalence and impact of LBBB on left ventricular mechanics using 2D strain imaging in patients with idiopathic dilated cardiomyopathy (IDCM). Methods: We included 101 patients with IDCM with mean age 38 ± 18 years: 74% were males and 13.9% of them were in NYHA Class III-IV. LBBB was present in 26 (37%) of included patients. Myocardial mechanics including longitudinal, circumferential strain and rotation and LV synchronization were assessed using two-dimensional strain imaging. Results: LBBB group had higher LV volumes, and PAP compared with non LBBB. Peak LV longitudinal systolic strain (εsys) of the septum and global LV SRsys were significantly lower in LBBB compared to non LBBB group (P 0.01, 0.03). TTP-d was greater in LBBB in comparison to non LBBB group (274.5 ± 116 versus 209.4 ± 139, P 0.02). The electromechanical delay between septal segments was 35 ± 18 ms and between lateral wall segments: 48 ± 24 ms, between anterior wall segments: 21 ± 11 and between inferior wall segments: 41 ± 12. Consequently, LV mechanical dyssynchrony was more evident in IDCM patients with LBBB. QRS width was correlated inversely with LV longitudinal strain and strain rate and electromechanical delay (P 0.0001) in non LBBB group. In LBBB QRS width was not related to cardiac mechanics. Using univariate analysis and after a multiple covariate adjustment, the baseline LBBB was associated with a significantly increased LV dysfunction. Conclusion:After correcting for potential confounders, LBBB was found to be associated with more deterioration of LV mechanics and exaggerated LV dyssynchrony in patients with IDCM.

Racial differences in prevalence and severity of non-alcoholic fatty liver disease

The aim of this review is to assess the evidence regarding racial differences in the prevalence and severity of nonalcoholic fatty liver disease(NAFLD).We reviewed the published literature that reported prevalence,severity,and genetic associations of NAFLD in different ethnic groups.The metabolic syndrome(MetS)has been associated with NAFLD,but each component of the MetS is present in various races in different percentages and their effect on NAFLD appears to be dissimilar.An elevated triglyceride(TG)level seems to have the strongest association with NAFLD.The latter is more prevalent in Hispanic patients;Blacks have lower TG levels and a lower NAFLD prevalence,compared to Caucasians or Hispanics.The severity of liver fibrosis is lower in some,but not all biopsy-based studies of Black patients.No study has evaluated the severity of liver disease controlling for the individual components of MetS,especially TG.Important racial differences in the prevalence of selected genetic polymorphisms,particularly PNPLA-3 and MBOAT7 have been documented,together with their effects on the prevalence of liver steatosis and fibrosis.Data on overall and liver mortality have found no significant differences according to race/ethnicity,with the possible exception of one paper reporting lower cirrhosis mortality in Black patients.We conclude that NAFLD is more prevalent in Hispanics and less in Blacks.This is supported by differences in key genetic polymorphisms associated with hepatic fat storage.However,there is presently insufficient evidence to firmly conclude that race,per se,plays a role in the development of liver fibrosis and its complications.Further studies,appropriately controlled for diet,exercise,and individual MetS parameters are needed.

Identification of various Biomphalaria alexandrina strains collected from five Egyptian governorates using RAPD and species-specific PCR techniques

The first generation of Biomphalaria snails collected from five Egyptian governorates (Giza, Fayoum, Kafr El-Sheikh, Ismailia and Damietta) were sub-jected to species-specific PCR assays and the results showed that snails collected from the field were B. alexandrina, and there was no evidence for the pres-ence of B. glabrata. The snails were subjected also to RAPD- PCR technique. The results showed that dif-ferent fingerprints with each B. alexandrina strain were produced with varying numbers of bands rang-ing in size from 123.6 to 796.6 bp depending on the snail strain and the primer used. Many specific bands were obtained with the four primers in each strain. Primer OPA-1 amplified the highest number of spe-cific bands (26 bands) and gave the highest poly-morphism among the primers used (100% polymor-phism). The estimated similarity coefficients among B. alexandrina strains based on the RAPD-PCR pro-files ranged from 0.56 to 0.72. The highest similarity coefficient (0.72) was recorded between the strains of Ismailia and Kafr El-Sheikh, while the lowest coeffi-cient (0.56) was reported between the strains of SPSC and Ismailia.

Reference Point Based TR-PSO for Multi-Objective Environmental/Economic Dispatch

A reference point based multi-objective optimization using a combination between trust region (TR) algorithm and particle swarm optimization (PSO) to solve the multi-objective environmental/economic dispatch (EED) problem is presented in this paper. The EED problem is handled by Reference Point Interactive Approach. One of the main advantages of the proposed approach is integrating the merits of both TR and PSO, where TR has provided the initial set (close to the Pareto set as possible and the reference point of the decision maker) followed by PSO to improve the quality of the solutions and get all the points on the Pareto frontier. The performance of the proposed algorithm is tested on standard IEEE 30-bus 6-genrator test system and is compared with conventional methods. The results demonstrate the capabilities of the proposed approach to generate true and well-distributed Pareto-optimal non-dominated solutions in one single run. The comparison with the classical methods demonstrates the superiority of the proposed approach and confirms its potential to solve the multi-objective EED problem.

General Cyclic Orthogonal Double Covers of Finite Regular Circulant Graphs

An orthogonal double cover (ODC) of a graph H is a collection of subgraphs (pages) of H, so that they cover every edge of H twice and the intersection of any two of them contains exactly one edge. An ODC G of H is cyclic (CODC) if the cyclic group of order is a subgroup of the automorphism group of G. In this paper, we introduce a general orthogonal labelling for CODC of circulant graphs and construct CODC by certain classes of graphs such as complete bipartite graph, the union of the co-cycles graph with a star, the center vertex of which, belongs to the co-cycles graph and graphs that are connected by a one vertex.