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AIM: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs) in hepatitis C virus (HCV) infected subjects with and without uremia. METHODS: Three subject groups were included in the study: group 1 involved 50 control subjects, group 2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by real-time polymerase chain reaction. Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All findings were correlated with disease activity, viral load and fibrogenesis. RESULTS: There was a significant decrease in co-stimulatory markers; CD83, CD86 and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were significantly higher in group 3 vs group 2. There was a significant elevation in PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs group 2. HA level was significantly correlated with disease activity and fibrosis grade in group 2. IL-10 was significantly correlated with fibrosis grade in group 2. There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a significant positive correlation between PD-L1 and viral load in both HCV groups. CONCLUSION: A significant decrease in DC co-stimulatory markers and a significant increase in a DC co-inhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients.

To evaluate the success rates, procedural time and adverse event rates of the modified methods in endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS).Twenty-eight patients in a prospective case series who underwent EUS-HGS (phase I). Forty-six patients in a matched case-control study (phase II). The simplified technique for fistula dilation was the primary use of a 4 mm balloon catheter with a stainless steel stylet. The stent deployment was modified by deploying the metal stent inside a bile duct (half of the stent) under EUS and fluoroscopic guidance and gently pulling the echoendoscope after full deployment of the stent inside the echoendoscope channel (remaining portion of the stent) under fluoroscopic guidance. This cohort was compared with a matched historical cohort.In phase I, the technical and clinical success with the modified method was 96% (27/28) and 89% (24/27 as per-protocol analysis). The overall adverse event rate was 7%. In phase II, there was no difference in technical and clinical success, stent patency and overall adverse events in each group. However, the procedural time (15.3 ± 5.2 min vs 22.3 ± 6.0 min, P0.001) and early adverse events (0% vs 26%, P = 0.02) were statistically improved in case cohort compared with control cohort.Compared with the conventional EUS-HGS technique, the procedural time was shorter and early adverse events were less frequent with our simplified and modified technique.

To elucidate the variety of ways early-stage hepatocellular carcinoma (HCC) can appear on magnetic resonance (MR) imaging by analyzing T1-weighted, T2-weighted, and gadolinium-enhanced dynamic studies.Seventy-three patients with well-differentiated HCC (wHCC) or dysplastic nodules were retrospectively identified from medical records, and new histological sections were prepared and reviewed. The tumor nodules were categorized into three groups: dysplastic nodule (DN), wHCC compatible with Edmondson-Steiner grade I HCC (w1-HCC), and wHCC compatible with Edmondson-Steiner grade II HCC (w2-HCC). The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.Among the 73 patients, 14 were diagnosed as having DN, 40 were diagnosed as having w1-HCC, and 19 were diagnosed as having w2-HCC. Hyperintensity measurements on T2-weighted axial images (T2WI) were statistically significant between DNs and wHCC (P = 0.006) and between DN and w1-HCC (P = 0.02). The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC. Hyperintensity on both T1W out-phase imaging (P = 0.007) and arterial enhancement on dynamic study (P = 0.005) showed statistically significant differences between w1-HCC and w2-HCC. The other imaging features revealed no significant differences between w1-HCC and w2-HCC.In the follow-up for a cirrhotic nodule, increased signal intensity on T2WI may be a sign of malignant transformation. Furthermore, a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.

To evaluate the red cell distribution width (RDW) as an indicator of the presence of non-alcoholic steatohepatitis (NASH) and its association with fibrotic scores.A retrospective study was carried out that included sixty-two biopsy proven NASH, 32 simple steatosis patients and 30 healthy controls. The correlation between the clinical and histopathological features of NASH patients and RDW values was evaluated. Liver fibrosis scores were measured using a 0 to 4 point scale and were divided in to two groups; fibrosis scores 0-1 were termed mild and fibrosis scores 2-4 were termed advanced fibrosis. RDW values were compared between NASH, simple steatosis and healthy controls. Univariate and multivariate analyses were performed to evaluate the independent predicting factors for the presence of liver fibrosis caused by NASH.Patients with NASH had higher RDW values compared with simple steatosis and healthy control groups [14.28% ± 0.25% vs 13.37% ± 0.12%, 12.96% ± 0.14% (P0.01), respectively]. Patients with advanced fibrosis had higher RDW values than the mild fibrosis group (15.86% ± 0.4% vs 13.63% ± 0.67%, P0.01, respectively). RDW also correlated with fibrotic scores (r = 0.579 and P0.01). The variables that were significant in the univariate analysis were evaluated in multivariate logistic regression analysis, and RDW was an independent predicting factor of NASH (OR = 1.75, 95%CI: 1.129-2.711, P0.05).RDW a new non-invasive marker that can be used to demonstrate the presence of NASH and indicate advanced fibrotic scores.

To investigate whether predicting patients that might be at a higher risk for complications might serve to improve the selection of patients undergoing colonic stenting.A retrospective review of consecutive patients who underwent an attempted self-expandable metal stent (SEMS) insertion for malignant colonic obstruction between November 2006 and March 2013. All patients were either referred for preoperative colonic decompression with the intent of a single surgical procedure, or for palliation of the malignant colorectal obstruction for unresectable cancer. Fisher's test or χ(2) test was performed on categorical variables, and the t test for continuous variables. Univariable and multivariable logistic regression were used to examine the association between independent variables and the presence of complications from SEMS insertion.SEMS insertion was attempted in 73 patients. Males comprised 55.71% and the mean age was 67.41 ± 12.41 years. Of these, 65.15% underwent subsequent surgery, while 34.85% received SEMS as palliation for advanced disease. Extracolonic tumors were only 4.76%. The majority of patients had stage IV disease (63.83%), while the remainder had stage III (36.17%). SEMS were successfully inserted in 93.85% (95%CI: 87.85%-99.85%). Perforations occurred in 4.10%, SEMS migration in 8.21%, and stent re-occlusion from ingrowth occurred in 2.74% of patients. The mean duration of follow up for the patients was 13.52 ± 17.48 mo (range 0-73 mo). None of the variables: age, sex, time between the onset of symptoms to SEMS insertion, time between SEMS insertion and surgery, length of the stenosis, location of the stenosis, albumin level, or receiving neoadjuvant chemotherapy, could predict the development of complications from either SEMS insertion nor prolonged survival.None of the variables could predict the development of complications or survival. Further studies are required to identify patients who would benefit the most from SEMS.

To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD).This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR)15 mL/min or end stage renal failure.Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P0.007). All 3 groups had significant reduction of proteinuria (P0.043, P0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P0.001).This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.

To assess the relationship between the P268S, JW1 and N852S polymorphisms and Crohn's disease (CD) susceptibility in Zhuang patients in Guangxi, China.Intestinal tissues from 102 Zhuang [48 CD and 54 ulcerative colitis (UC)] and 100 Han (50 CD and 50 UC) unrelated patients with inflammatory bowel disease and 72 Zhuang and 78 Han unrelated healthy individuals were collected in the Guangxi Zhuang Autonomous Region from January 2009 to March 2013. Genomic DNA was extracted using the phenol chloroform method. The P268S, JW1 and N852S polymorphisms were amplified using polymerase chain reaction (PCR), detected by restriction fragment length polymorphism (RFLP), and verified by gene sequencing.Heterozygous mutation of P268S in the NOD2/CARD15 gene was detected in 10 CD cases (six Zhuang and four Han), two Han UC cases, and one Zhuang healthy control, and P268S was strongly associated with the Chinese Zhuang and Han CD populations (P = 0.016 and 0.022, respectively). No homozygous mutant P268S was detected in any of the groups. No significant difference was found in P268S genotype and allele frequencies between UC and control groups (P0.05). Patients with CD who carried P268S were likely to be ≤ 40 years of age (P = 0.040), but were not significantly different with regard to race, lesion site, complications, and other clinical features (P0.05). Neither JW1 nor N852S polymorphisms of the NOD2/CARD15 gene were found in any of the subjects (P0.05).P268S polymorphism may be associated with CD susceptibility in the Zhuang population in the Guangxi Zhuang Autonomous Region, China. In contrast, JW1 and N852S polymorphisms may not be related to CD susceptibility in these patients.

AIM: To identify potential biomarkers of primary gallbladder cancer (PGC). METHODS: Fresh PGC, cholecystitis and normal gallbladder tissue specimens collected from 10 patients, respectively, were subjected to comparative proteomic analysis. The proteomic patterns of PGC were compared with those of cholecystitis and normal gallbladder tissues using two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were then identified using a MALDI-TOF mass spectrometer (MS) and database searches. To further validate these proteins, 20 samples of PGC tissues and normal tumor-adjacent tissues were collected for Western blot, quantitative real-time PCR, and immunohistochemical staining assay. RESULTS: Seven differentially expressed protein spots were detected by 2-ED analysis by comparing the average maps of PGC, cholecystitis and normal gallbladder tissues. Six of the seven differentially expressed proteins were identified using MALDI-TOF MS, with three overexpressed and three underexpressed in PGC tissue. Protein levels of annexin A4 (ANXA4) were significantly elevated, and heat shock protein 90-beta (Hsp90β) and dynein cytoplasmic 1 heavy chain 1 (Dync1h1) were decreased in PGC tissues relative to the normal tumor-adjacent tissues as shown by Western blot analysis. However, levels of actin, aortic smooth muscle and gamma-actin were unchanged. In addition, the mRNA levels of all 5 proteins showed similar changes to those of the protein levels (P < 0.01). Further validation by immunohistochemical analysis showed the upregulated expression of ANXA4 and decreased expression of Hsp90β and Dync1h1 in the cytoplasm of PGC tissues relative to the normal tumor-adjacent tissues. CONCLUSION: Three proteins are identified as potential biomarkers of PGC using proteomic analysis. The functions of these proteins in the carcinogenesis of PGC remain to be studied.

To identify the relationship between tag single nucleotide polymorphisms (tag SNPs) of interleukin-6 (IL-6) gene and susceptibility to chronic hepatitis B virus (HBV) infection in a Han Chinese population.We performed a case-control study of 501 Chinese patients with chronic HBV infection and 301 self-limiting HBV-infected individuals as controls. Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract high-density tubes. Tag SNPs were identified using genotype data from the panel (Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6 (rs17147230A/T, rs2066992G/T, rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed.Five haplotypes were involved in the analysis, with frequencies higher than 0.03. One of the haplotypes, TTAA, was significantly different between the two groups. Overall haplotype P values were: ATAA, P = 0.605, OR (95%CI) = 1.056 (0.860-1.297); TGAG, P = 0.385, OR (95%CI) = 1.179 (0.813-1.709); TGGG, P = 0.549, OR (95%CI) = 1.087 (0.827-1.429); TTAA, P = 0.004, OR (95%CI) = 0.655 (0.491-0.873); TTAG, P = 0.266, OR (95%CI) = 1.272 (0.832-1.944). However, the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were: rs17147230, P = 0.696, OR (95%CI) = 1.041 (0.850-1.276); rs2066992, P = 0.460, OR (95%CI) = 1.090 (0.868-1.369); rs2069837, P = 0.898, OR (95%CI) = 0.983 (0.759-1.274); rs2069852, P = 0.165, OR (95%CI) = 0.859 (0.693-1.064). Overall genotype P values were: rs17147230, P = 0.625; rs2066992, P = 0.500; rs2069837, P = 0.853; and rs2069852, P = 0.380.The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population.

To determine the expression of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and the Ku70/Ku80 heterodimer (Ku 70/80) in gastric carcinoma.Gastric biopsies were obtained from 146 gastric carcinoma patients [Helicobacter pylori (H. pylori)-negative: 89 and H. pylori-positive: 57] and 34 from normal subjects (H. pylori-negative: 16 and H. pylori-positive: 18) via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University. Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system. An ''in-house'' rapid urease test and modified Giemsa staining were employed to detect H. pylori infection. The expression of DNA-PKcs and the Ku 70/80 protein was detected by immunohistochemistry.Overall, the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer (χ(2) = 133.04, P0.001 for DNA-PKcs and χ(2) = 13.06, P0.01 for Ku) compared with normal gastric mucosa. There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa, and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0% (0/34), whereas the rate in gastric cancer (GC) was 93.8% (137/146). The difference between the two groups was statistically significant. Additionally, the positive rate of Ku 70/80 was 79.4% (27/34) in normal gastric mucosa and 96.6% (141/146) in gastric cancer. The DNA-PKcs protein level was significantly increased in gastric cancer (Mann-Whitney U = 39.00, P0.001), compared with normal gastric mucosa. In addition, there was a significant difference in the expression of Ku 70/80 (Mann-Whitney U = 1117.00, P0.001) between gastric cancer and normal gastric mucosa. There was also a significant difference in Ku70/80 protein expression between GC patients with and without H. pylori infection (P0.05). Spearman analysis showed a negative correlation between tumor differentiation and DNA-PKcs expression (r = -0.447, P0.05). Moreover, Ku70/80 expression was negatively correlated with both clinical stage (r = -0.189, P0.05) and H. pylori colonization (r = -0.168, P0.05).Overall, this research demonstrated that enhanced DNA-PKcs and Ku 70/80 expression may be closely associated with gastric carcinoma.

To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack.We studied vascular reactivity in the resistance arteries by using the forearm perfusion technique associated with plethysmography. We measured forearm blood flow by strain-gauge plethysmography during intra-brachial infusion of acetylcholine, sodium nitroprusside or norepinephrine in 11 controls and 13 patients with migraine, 11 of them (M) in the interval between the migraine attacks and 4 during a headache attack (MH). Written informed consent was obtained from patients and healthy controls, and the study was approved by the Ethics Committee of the University Federico II.Compared to healthy control subjects, in patients with migraine studied during the interictal period, the vasodilating effect of acetylcholine, that acts through the stimulation of endothelial cells and the release of nitric oxide, was markedly reduced, but became normal during the headache attack (P < 0.05 by analysis of variance). The response to nitroprusside, which directly relaxes vascular smooth muscle cells (VSMCs), was depressed in patients with migraine studied during the interictal period, but normal during the headache attack (P < 0.005). During norepinephrine infusion, forearm blood flow decreased in control subjects (-40% ± 5%, P < 0.001). In contrast, in patients with migraine, either when studied during or free of the headache attack forearm blood flow did not change compared to the baseline value (-3% ± 13% and -10.4% ± 15%, P > 0.05).In migrainers, the impaired relaxation of VSMCs is restored during the headache attack. The vasoconstrictory response is impaired and remains unchanged during the migraine attack.

Human pancreatic ribonuclease (RNase 1) is a small secretory protein that catalyzes the cleavage of RNA. This highly cationic enzyme can enter human cells spontaneously but is removed rapidly from circulation by glomerular filtration. Here, this shortcoming is addressed by attaching a poly(ethylene glycol) (PEG) moiety to RNase 1. The pendant has no effect on ribonucleolytic activity but does increase persistence in circulation. The RNase 1-PEG conjugates inhibit the growth of tumors in a xenograft mouse model of human lung cancer. Both retention in circulation and tumor growth inhibition correlate with the size of the pendant PEG. A weekly dose of the 60-kDa conjugate at 1 µmol/kg inhibited nearly all tumor growth without affecting body weight. Its molecular efficacy is ∼5000-fold greater than that of erlotinib, which is a small molecule in clinical use for the treatment of lung cancer. These data demonstrate that the addition of a PEG moiety can enhance the in vivo efficacy of human proteins that act within cells and highlight a simple means of converting an endogenous human enzyme into a cytotoxin with potential clinical utility.

To investigate the relationship between increases in expression time of ABCG2 mRNA driven by cisplatin and efficacy of platinum-containing chemotherapy for gastric cancer.Tumor specimens and normal control tissues were collected from 78 patients with gastric cancer treated from January 2008 to December 2011. Fresh tumor tissue obtained from the surgically resected specimens was tested within 6 h. Polymerase chain reaction products were run on 2% agarose gels and analyzed under ultraviolet light after ethidium bromide staining. Increases in ABCG2 mRNA expression time were assessed after cancer cells were incubated with cisplatin, and were divided into terciles and compared in relation to clinical outcomes.Among groups classified by expression time of ABCG2 mRNA, no significant differences in baseline clinical characteristics and pathological findings were detected. The median overall time was 14.2 (95%CI: 9.7-18.6), 11.4 (95%CI: 6.3-16.5) and 8.1 (95%CI: 5.4-10.8) in patients with low, intermediate and high increases in ABCG2 mRNA expression times (P0.05), respectively. Median survival associated with performance status and tumor node metastasis (TNM) stage showed a similar trend, with longer survival and higher risk for mortality associated with lower performance status score and TNM stage. In a multivariate analysis for survival with Cox proportional-hazards model, increased ABCG2 mRNA expression time was an independent predictor for overall survival. Overall survival was longer with increased ABCG2 mRNA expression times ≤ 0.71 than increased ABCG2 mRNA expression times0.71, with a hazard ratio for death of 0.855 (95%CI: 0.615-0.962, P = 0.038).Increased ABCG2 mRNA expression time driven by cisplatin is associated with survival of gastric cancer patients, and this may help modify the therapeutic strategies.

AIM: To investigate expression of stem cell marker Musashi-1 (Msi-1) in relationship to tumorigenesis and progression of intestinal-type gastric cancer (GC). METHODS: Endoscopic biopsy specimens and surgical specimens were obtained, including 54 cases of intestinal-type GC, 41 high-grade intraepithelial neoplasia, 57 low-grade intraepithelial neoplasia, 31 intestinal metaplasia, and 36 normal gastric mucosa. Specimens were fixed in 10% paraformaldehyde, conventionally dehydrated, embedded in paraffin, and sliced in 4-μm-thick serial sections. Two-step immunohistochemical staining was used to detect Msi-1 and proliferating cell nuclear antigen (PCNA) expression. Correlation analysis was conducted between Msi-1 and PCNA expression. The relationship between Msi-1 expression and clinicopathological parameters of GC was analyzed statistically. RESULTS: There were significant differences in Msi-1 and PCNA expression in different pathological tissues (χ2 = 15.37, P < 0.01; χ2 = 115.36, P < 0.01). Msi-1 and PCNA-positive cells were restricted to the isthmus of normal gastric glands. Expression levels of Msi-1 and PCNA in intestinal metaplasia were significantly higher than in normal mucosa (U = 392.0, P < 0.05; U = 40.50, P < 0.01), whereas there was no significant difference compared to low or high-grade intraepithelial neoplasia. Msi-1 and PCNA expression in intestinal-type GC was higher than in high-grade intraepithelial neoplasia (U = 798.0, P < 0.05; U = 688.0, P < 0.01). There was a significantly positive correlation between Msi-1 and PCNA expression (rs = 0.20, P < 0.01). Msi-1 expression in GC tissues was correlated with their lymph node metastasis and tumor node metastasis stage (χ2 = 12.62, P < 0.01; χ2 = 11.24, P < 0.05), but not with depth of invasion and the presence of distant metastasis. CONCLUSION: Msi-1-positive cells may play a key role in the early events of gastric carcinogenesis and may be involved in invasion and metastasis of GC.

AIM: To investigate current preferences and opinions on the diagnosis, treatment and rehabilitation of patients with anterior cruciate ligament (ACL) injury in Croatia. ----- METHODS: The survey was conducted using a questionnaire which was sent by e-mail to all 189 members of the Croatian Orthopaedic and Traumatology Association. Only respondents who had performed at least one ACL reconstruction during 2011 were asked to fill out the questionnaire. ----- RESULTS: Thirty nine surgeons responded to the survey. Nearly all participants (95%) used semitendinosus/gracilis tendon autograft for reconstruction and only 5% used bone-patellar tendon-bone autograft. No other graft type had been used. The accessory anteromedial portal was preferred over the transtibial approach (67% vs 33%). Suspensory fixation was the most common graft fixation method (62%) for the femoral side, followed by the cross-pin (33%) and bioabsorbable interference screw (5%). Almost all respondents (97%) used a bioabsorbable interference screw for tibial side graft fixation. ----- CONCLUSION: The results show that ACL reconstruction surgery in Croatia is in step with the recommendations from latest world literature.

To present the 18 year survival and the clinical and radiological outcomes of the Müller straight stem, cemented, total hip arthroplasty (THA).Between 1989 and 2007, 176 primary total hip arthroplasties in 164 consecutive patients were performed in our institution by the senior author. All patients received a Müller cemented straight stem and a cemented polyethylene liner. The mean age of the patients was 62 years (45-78). The diagnosis was primary osteoarthritis in 151 hips, dysplasia of the hip in 12 and subcapital fracture of the femur in 13. Following discharge, serial follow-up consisted of clinical evaluation based on the Harris Hip Score and radiological assessment. The survival of the prosthesis using revision for any reason as an end-point was calculated by Kaplan-Meier analysis.Twenty-four (15%) patients died during the follow-up study, 6 (4%) patients were lost, while the remaining 134 patients (141 hips) were followed-up for a mean of 10 years (3-18 years). HSS score at the latest follow-up revealed that 84 hips (59.5%) had excellent results, 30 (22.2%) good, 11 (7.8%) fair and 9 (6.3%) poor. There were 3 acetabular revisions due to aseptic loosening. Six (4.2%) stems were diagnosed as having radiographic definitive loosening; however, only 1 was revised. 30% of the surviving stems showed no radiological changes of radiolucency, while 70% showed some changes. Survival of the prosthesis for any reason was 96% at 10 years and 81% at 18 years.The 18 year survival of the Müller straight stem, cemented THA is comparable to those of other successful cemented systems.

AIM: To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2 (HER2) antibodies in whole-tissue sections and tissue microarrays (TMAs) of a series of gastric tumors. METHODS: We present a comparative analysis of three anti-HER2 antibodies (HercepTest, 4B5 and SP3) using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December 2008 at a Brazilian cancer hospital. The data on the patients’ age, sex, the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records. The immunohistochemical (IHC) results were examined by two pathologists and the cases were classified as positive (3+), equivocal (2+) and negative (0 or 1+), according to the criteria of the IHC scoring system of gastric cancer. TMAs and whole-tissue sections were evaluated separately and independently. All cases yielding discordant IHC results and/or scored as 2+ were subjected to dual-color in situ hybridization in order to determine the final HER2 status. Besides determining the sensitivity and predictive value for HER2-positive status, we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic (ROC) curve. The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient. RESULTS: Intratumoral heterogeneity of HER2 expression was observed with all antibodies. HER2-positive expression (3+) in the whole-tissue sections was observed in 23 cases (11.6%) using the 4B5 antibody, in 18 cases (9.1%) using the SP3 antibody and in 10 cases (5.1%) using the HercepTest antibody. In the TMAs, 11 positive cases (5.6%) were identified using SP3 antibody, 9 (4.6%) using the 4B5 antibody and 6 (3%) using the HercepTest antibody. The sensitivity using whole-tissue sections and TMA, respectively, was 95.2% and 42.9% with 4B5, 90.5% and 66.7% with SP3 and 47.6% and 42.9% with HercepTest. The accuracy, calculated from the area under the ROC curve, using whole-tissue sections and TMA, respectively, was 0.91 and 0.79 by 4B5, 0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest. The concordance of the results obtained using whole-tissue sections and TMA was 97.4% (Kappa 0.75) using HercepTest, 85.6% (Kappa 0.56) using SP3 and 84.1% (Kappa 0.38) using 4B5. CONCLUSION: The use of the 4B5 antibody on whole-tissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.

AIM: To explore the association between consumption of spicy foods and prevalence of irritable bowel syndrome (IBS) among Iranian adults. METHODS: In this cross-sectional study, data from 4763 Iranian adult participants were used. Consumption of spicy foods was estimated using a dietary habits questionnaire that included a question on spicy foods consumption: “how frequently do you use spicy foods (pepper, curry, ginger, cinnamon and turmeric) during a week?” Participants could respond to the question by choosing one of these choices: never, 1-3 times, 4-6 times, 7-9 times, or more than 10 times per week. A modified Persian version of the Rome III questionnaire was used to determine the prevalence of IBS. RESULTS: IBS was prevalent in 21.7% (18.6% of men and 24.1% of women) of the study population. After controlling for potential confounders including dietary behaviors, those consuming spicy foods ≥ 10 times per week were 92% more likely to have IBS compared with those who never consumed spicy foods (OR = 1.92; 95%CI: 1.23-3.01, Ptrend < 0.01). The association remained significant even after taking lactose intolerance into account (OR = 1.85; 95%CI: 1.18-2.90, Ptrend < 0.01). Stratified analysis by gender revealed that the association between consumption of spicy foods and IBS was not significant in men; however, a significant association was found among women after taking potential cofounders, including meal regularity and lactose intolerance, into account. Women who consumed spicy foods ≥ 10 times per week were two times more likely to have IBS compared with those who never consumed spicy foods (OR = 2.03; 95%CI: 1.09-3.77, Ptrend = 0.02). CONCLUSION: Consumption of spicy foods is directly associated with IBS, particularly in women. Further, prospective studies are warranted to (1) examine this association in other populations; and (2) evaluate whether dietary interventions, for example a reduction in spice consumption, would improve IBS symptoms.

AIM: To investigate whether routinely measured clinical variables could aid in differentiating intestinal tuberculosis (ITB) from Crohn’s disease (CD). METHODS: ITB and CD patients were prospectively included at four South Indian medical centres from October 2009 to July 2012. Routine investigations included case history, physical examination, blood biochemistry, ileocolonoscopy and histopathological examination of biopsies. Patients were followed-up after 2 and 6 mo of treatment. The diagnosis of ITB or CD was re-evaluated after 2 mo of antituberculous chemotherapy or immune suppressive therapy respectively, based on improvement in signs, symptoms and laboratory variables. This study was considered to be an exploratory analysis. Clinical, endoscopic and histopathological features recorded at the time of inclusion were subject to univariate analyses. Disease variables with sufficient number of recordings and P < 0.05 were entered into logistic regression models, adjusted for known confounders. Finally, we calculated the odds ratios with respective confidence intervals for variables associated with either ITB or CD. RESULTS: This study included 38 ITB and 37 CD patients. Overall, ITB patients had the lowest body mass index (19.6 vs 22.7, P = 0.01) and more commonly reported weight loss (73% vs 38%, P < 0.01), watery diarrhoea (64% vs 33%, P = 0.01) and rural domicile (58% vs 35%, P < 0.05). Endoscopy typically showed mucosal nodularity (17/31 vs 2/37, P < 0.01) and histopathology more frequently showed granulomas (10/30 vs 2/35, P < 0.01). The CD patients more frequently reported malaise (87% vs 64%, P = 0.03), nausea (84% vs 56%, P = 0.01), pain in the right lower abdominal quadrant on examination (90% vs 54%, P < 0.01) and urban domicile (65% vs 42%, P < 0.05). In CD, endoscopy typically showed involvement of multiple intestinal segments (27/37 vs 9/31, P < 0.01). Using logistic regression analysis we found weight loss and nodularity of the mucosa were independently associated with ITB, with adjusted odds ratios of 8.6 (95%CI: 2.1-35.6) and 18.9 (95%CI: 3.5-102.8) respectively. Right lower abdominal quadrant pain on examination and involvement of ≥ 3 intestinal segments were independently associated with CD with adjusted odds ratios of 10.1 (95%CI: 2.0-51.3) and 5.9 (95%CI: 1.7-20.6), respectively. CONCLUSION: Weight loss and mucosal nodularity were associated with ITB. Abdominal pain and excessive intestinal involvement were associated with CD. ITB and CD were equally common.

AIM: To evaluate the efficacy and safety of grasper type scissors (GTS) for endoscopic submucosal dissection (ESD) of gastric epithelial neoplasia. METHODS: The study was performed by 4 endoscopists in 4 institutions affiliated to The Catholic University of Korea. ESD was performed in 76 consecutive patients with gastric epithelial neoplasia by using the GTS (37 patients) or the hook knife plus coagrasper (HKC) (39 patients). The complete resection rate, complication rate, total time elapsed and elapsed time per square centimeter of the dissected specimen were analyzed between the GTS and HKC group. RESULTS: The mean age of the GTS group was 62.3 ± 11.4 years and mean age of the HKC group was 65.6 ± 10.1 years. Differentiated adenocarcinoma was found in 32.4% in the GTS group and 33.3% in the HKC group. The procedures were performed without interruption in every case in both groups. The en bloc resection rates of both groups were 100%. The total time elapsed during the procedure was 44.54 ± 21.72 min in the GTS group and 43.77 ± 21.84 min in the HKC group (P = 0.88) and the time elapsed per square centimeter of the resected lesion was 7.53 ± 6.35 min/cm2 in the GTS group and 6.92 ± 5.93 min/cm2 in the HKC group (P = 0.66). The overall complication rate was not significantly different between the two groups. CONCLUSION: GTS is a safe and effective device for ESD compared with HKC. ESD can be performed with GTS alone, which can reduce the costs for ESD.

To investigate the effects of nilotinib in a rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis.Twenty-one Wistar albino female rats obtained from Dokuz Eylul University Department of Laboratory Animal Science were categorized into a control (n = 7), TNBS (n = 7) and nilotinib group (n = 7). Saline was administered orally for 14 d to the control and the TNBS group. The TNBS group received rectal TNBS on the first day while saline was administered to the control group. The nilotinib group received 20 mg/kg nilotinib for 14 d in 2 divided doses, starting the same day as TNBS administration. For 14 d, the rats were fed a standard diet, and their weights were recorded daily. After sacrifice, colon tissue samples from each group were scored for macroscopic and microscopic pathology. Apoptotic indices were determined by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method. Platelet-derived growth factor receptor (PDGFR) alpha and beta levels were assessed through immunohistochemistry staining scores and compared among the groups. Tissue and serum tumor necrosis factor (TNF) alpha levels were determined by enzyme-linked immunosorbent assay.Between days 1 and 14, the nilotinib group rats lost significantly less weight than the TNBS group rats (-0.7 g vs -14.0 g, P = 0.047). The difference in weight between the control and nilotinib groups was also statistically significant (+8.3 g vs -0.7 g, P = 0.031). From day 7 to day 14, the weight differences of the control group vs the TNBS group, the TNBS group vs the nilotinib group, and the control group vs the nilotinib group were all statistically significant (+8.0 g vs -11.1 g, P = 0.007; -11.1 g vs +2.9 g, P = 0.015; +8.0 g vs +2.9 g, P = 0.042, respectively). Macroscopic and microscopic scores were significantly lower in the nilotinib group than in the TNBS group (0.00 ± 0.00 vs 1.43 ± 0.65, P = 0.009; 2.86 ± 0.55 vs 7.71 ± 1.48, P = 0.030, respectively). However, these scores were similar between the nilotinib and control groups. While no significant difference for the nilotinib vs control groups could be determined for PDGFR alpha and beta scores, PDGFR alpha and beta scores were lower in the nilotinib group than in the TNBS group. Furthermore, the TNF alpha levels in the serum, tissue and apoptosis scores were similar between the nilotinib and TNBS groups.Nilotinib prevents weight loss, facilitates mucosal healing by improving the pathological scores without introducing variation into the apoptotic scores or TNF alpha levels.

AIM: To study serological antibodies in Caucasians and Asians, in health and inflammatory bowel disease (IBD), in Australia and Hong Kong (HK). METHODS: Anti-glycan antibodies [anti-chitobioside (ACCA), anti-laminaribioside (ALCA)], and anti-mannobioside (AMCA), anti-Saccharomyces cervisiae (gASCA); and atypical perinuclear anti-neutrophil cytoplasmic antibody (pANCA) were tested in IBD patients, their unaffected relatives, and healthy controls in Australia and HK (China). Antibody status (positive or negative) and titre was compared between subjects of different geography, ethnicity and disease state. RESULTS: Ninety subjects were evaluated: 21 Crohn’s disease (CD), 32 ulcerative colitis (UC), 29 healthy controls, and 8 IBD patient relatives. Forty eight subjects were Australian (29 Caucasian and 19 ethnic Han Chinese) and 42 were from HK (all Han Chinese). Caucasian CD patients had a significantly higher antibody prevalence of gASCA (67% vs 3%, P < 0.001), ALCA (44% vs 6%, P = 0.005), and AMCA (67% vs 15%, P = 0.002), whereas HK CD patients had a higher prevalence of only AMCA (58% vs 25%, P = 0.035), when compared with UC and healthy subjects in both countries. Caucasian CD had significantly higher gASCA prevalence (67% vs 0%, P < 0.001) and titre (median 59 vs 9, P = 0.002) than HK CD patients. Prevalence and titres of ALCA, ACCA and AMCA did not differ between CD in the two countries. Presence of at least one antibody was higher in Caucasian than HK CD patients (100% vs 58%, P = 0.045). pANCA did not differ between countries or ethnicity. CONCLUSION: Serologic CD responses differ between HK Asian and Australian Caucasian patients. Different genetic, environmental or disease pathogenic factors may account for these differences.

AIM: To investigate adjuvant chemotherapy, p53 and carcinoembryonic antigen (CEA) expression and prognosis after D2 gastrectomy for stage II/III gastric adenocarcinoma. METHODS: A total of 286 patients with stage II or III gastric adenocarcinoma who underwent D2 radical gastrectomy between May 2007 and December 2010 were enrolled into this study. One hundred and sixty-nine of these patients received surgery plus adjuvant chemotherapy, and 117 patients received surgery alone. Tumor expression of p53 and CEA proteins in all patients was evaluated immunohistochemically and correlated with clinicopathological parameters. The Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) with log-rank testing were used to compare the survival difference. A Cox proportional hazard regression model was used for multivariate analysis. RESULTS: Patients with adjuvant chemotherapy had a significantly better median OS (50.87 mo vs 30.73 mo, P = 0.000) and median DFS (36.30 mo vs 25.60 mo, P = 0.001) than patients with surgery alone in the entire cohort. Consistent results with the entire cohort were found in stage II (P = 0.006 and P = 0.047), stage III (P = 0.005 and P = 0.030), and stage IIIB/IIIC patients (P = 0.000 and P = 0.001). The median OS and DFS advantages were confirmed by multivariate analysis (P = 0.000 and P = 0.008) and maintained when the analyses were restricted to fluoropyrimidine monotherapy (P = 0.003 and P = 0.001) and fluoropyrimidine plus platinum regimen (P = 0.001 and P = 0.007), however, not the fluoropyrimidine plus taxane (P = 0.198 and P = 0.777) or platinum plus taxane (P = 0.666 and P = 0.687) regimens. Median OS and median DFS did not differ significantly between the patients with p53(+) and p53(-) tumors (P = 0.608 and P = 0.064), or between patients with CEA(+) and CEA(-) tumors (P = 0.052 and P = 0.989), which were maintained when the analyses were restricted to surgery alone (p53: P = 0.864 and P = 0.431; CEA: P = 0.142 and P = 0.948), adjuvant chemotherapy (p53: P = 0.802 and P = 0.091; CEA: P = 0.223 and P = 0.946) and even different chemotherapy regimens (P > 0.05). CONCLUSION: Patients after D2 gastrectomy for stage II/III gastric adenocarcinoma had significantly better survival after fluoropyrimidine monotherapy and fluoropyrimidine plus platinum. p53 and CEA were not prognostic.

AIM: To study a retrospective analysis of patients who presented to the emergency departments (ED) with complaints related to foreign body ingestions. METHODS: Patients older than 16 years of age who presented to the ED between January 1st and December 31st of 2010 with complaints related to swallowed foreign bodies were identified from electronic health records and patient charts. RESULTS: A total of 100 patients presented with a complaint of foreign body ingestion during the study period. Overall, an X-ray was performed on 75 patients, and a fiberoptic evaluation was performed on 45 patients. A foreign body was detected in 46 (46%) patients. The diagnostic yield of the X-ray was 27 (36%) out of 75 patients, while the diagnostic yield of the fiberoptic evaluations was 21 (47%) out of 45 patients. The detected foreign bodies were mostly located in the esophagus (17 out of 46 foreign bodies detected). When the types of ingested foreign bodies were evaluated, 52 (52%) patients reported ingesting food, and 19 (19%) patients reported swallowing pins. An X-ray was performed on 33 patients with accidental food ingestions but yielded a positive result in only two cases. In 12 out of 21 patients with accidental food ingestion who underwent fiberoptic evaluation, the foreign material was detected and removed. CONCLUSION: Plain radiography is helpful in the localization of radiopaque swollen foreign bodies, while fiberoptic methods are useful as both diagnostic and therapeutic tools, regardless of radiopacity. (C) 2013 Baishideng. All rights reserved.

AIM: To explore whether computer tomography coronary angiography (CTCA) using iterative reconstruction (IR) leads to significant radiation dose reduction without a significant loss in image interpretability compared to conventional filtered back projection (FBP). METHODS: A consecutive series of 200 patients referred to our institution to undergo CTCA constituted the study population. Patients were sequentially assigned to FBP or IR. All studies were acquired with a 256-slice CT scanner. A coronary segment was considered interpretable if image quality was adequate for evaluation of coronary lesions in all segments ≥ 1.5 mm. RESULTS: The mean age was 56.3 ± 9.6 years and 165 (83%) were male, with no significant differences between groups. Most scans were acquired using prospective ECG triggering, without differences between groups (FBP 84% vs IR 82%; P = 0.71). A total of 3198 (94%) coronary segments were deemed of diagnostic quality. The percent assessable coronary segments was similar between groups (FBP 91.7% ± 4.0% vs IR 92.5% ± 2.8%; P = 0.12). Radiation dose was significantly lower in the IR group (2.8 ± 1.4 mSv vs 4.6 ± 3.0 mSv; P < 0.0001). Image noise (37.8 ± 1.4 HU vs 38.2 ± 2.4 HU; P = 0.20) and signal density (461.7 ± 51.9 HU vs 462.2 ± 51.2 HU; P = 0.54) levels did not differ between FBP and IR groups, respectively. The IR group was associated to significant effective dose reductions, irrespective of the acquisition mode. CONCLUSION: Application of IR in CTCA preserves image interpretability despite a significant reduction in radiation dose. Fil: Carrascosa, Patricia. Diagnóstico Maipú; Argentina Fil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Capuñay, Carlos. Diagnóstico Maipú; Argentina Fil: Deviggiano, Alejandro. Diagnóstico Maipú; Argentina

To evaluate outcomes of radiofrequency ablation (RFA) therapy for early hepatocellular carcinoma (HCC) and identify survival- and recurrence-related factors.Consecutive patients diagnosed with early HCC by computed tomography (CT) or magnetic resonance imaging (MRI) (single nodule of ≤ 5 cm, or multi- (up to 3) nodules of ≤ 3 cm each) and who underwent RFA treatment with curative intent between January 2010 and August 2011 at the Instituto do Câncer do Estado de São Paulo, Brazil were enrolled in the study. RFA of the liver tumors (with 1.0 cm ablative margin) was carried out under CT-fluoro scan and ultrasonic image guidance of the percutaneous ablation probes. Procedure-related complications were recorded. At 1-mo post-RFA and 3-mo intervals thereafter, CT and MRI were performed to assess outcomes of complete response (absence of enhancing tissue at the tumor site) or incomplete response (enhancing tissue remaining at the tumor site). Overall survival and disease-free survival rates were estimated by the Kaplan-Meier method and compared by the log rank test or simple Cox regression. The effect of risk factors on survival was assessed by the Cox proportional hazard model.A total of 38 RFA sessions were performed during the study period on 34 patients (age in years: mean, 63 and range, 49-84). The mean follow-up time was 22 mo (range, 1-33). The study population showed predominance of male sex (76%), less severe liver disease (Child-Pugh A, n = 26; Child-Pugh B, n = 8), and single tumor (65%). The maximum tumor diameters ranged from 10 to 50 mm (median, 26 mm). The initial (immediately post-procedure) rate of RFA-induced complete tumor necrosis was 90%. The probability of achieving complete response was significantly greater in patients with a single nodule (vs patients with multi-nodules, P = 0.04). Two patients experienced major complications, including acute pulmonary edema (resolved with intervention) and intestinal perforation (led to death). The 1- and 2-year overall survival rates were 82% and 71%, respectively. Sex, tumor size, initial response, and recurrence status influenced survival, but did not reach the threshold of statistical significance. Child-Pugh class and the model for end-stage liver disease score were identified as predictors of survival by simple Cox regression, but only Child-Pugh class showed a statistically significant association to survival in multiple Cox regression analysis (HR = 15; 95%CI: 3-76 mo; P = 0.001). The 1- and 2-year cumulative disease-free survival rates were 65% and 36%, respectively.RFA is an effective therapy for local tumor control of early HCC, and patients with preserved liver function are the best candidates.

AIM: To explore the feasibility and safety of endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy (LC) performed during the same session. METHODS: Between July 2010 and May 2013, 156 patients with gallstones and common bile duct (CBD) stones were enrolled in this retrospective study. According to the sequence of endoscopic procedures and LC, patients were classified into two groups: in group 1, patients underwent endoscopic stone extraction and LC during the same session, and in group 2, patients underwent LC at least 3 d after endoscopic stone extraction. Outcomes of the endoscopic procedures and LC were compared between the two groups, respectively. RESULTS: There were 91 patients in group 1 and 65 patients in group 2. The characteristics of the two groups were similar. The mean duration of the endoscopic procedures was 34.9 min in group 1 and 35.3 min in group 2. There were no significant differences in the success rate of the endoscopic procedures (97.8% for group 1 vs 98.5% for group 2), the total rate of endoscopic complications (4.40% for group 1 vs 4.62% for group 2) and CBD stone clearance rate (96.7% for group 1 vs 96.9% for group 2). Duration of LC was 53.6 min in group 1 and 52.8 min in group 2. There were no significant differences in the overall LC-related morbidity and postoperative hospital stay. CONCLUSION: Endoscopic stone extraction and LC performed during the same session was feasible and safe in patients with gallstones and concomitant CBD stones.

AIM: To investigate the dynamic features of insulin-like growth factor-I receptor (IGF-IR) expression in rat hepatocarcinogenesis, and the relationship between IGF-IR and hepatocytes malignant transformation at mRNA or protein level. METHODS: Hepatoma models were made by inducing with 2-fluorenylacetamide (2-FAA) on male Sprague-Dawley rats. Morphological changes of hepatocytes were observed by pathological Hematoxylin and eosin staining, the dynamic expressions of liver and serum IGF-IR were quantitatively analyzed by an enzyme-linked immunosorbent assay. The distribution of hepatic IGF-IR was located by immunohistochemistry. The fragments of IGF-IR gene were amplified by reverse transcription-polymerase chain reaction, and confirmed by sequencing. RESULTS: Rat hepatocytes after induced by 2-FAA were changed dynamically from granule-like degeneration, precancerous to hepatoma formation with the progressing increasing of hepatic mRNA or IGF-IR expression. The incidences of liver IGF-IR, IGF-IR mRNA, specific IGF-IR concentration (ng/mg wet liver), and serum IGF-IR level (ng/mL) were 0.0%, 0.0%, 0.63 ± 0.17, and 1.33 ± 0.47 in the control; 50.0%, 61.1%, 0.65 ± 0.2, and 1.51 ± 0.46 in the degeneration; 88.9%, 100%, 0.66 ± 0.14, and 1.92 ± 0.29 in the precancerosis; and 100%, 100%, 0.96 ± 0.09, and 2.43 ± 0.57 in the cancerous group, respectively. IGF-IR expression in the cancerous group was significantly higher (P < 0.01) than that in any of other groups at mRNA or protein level. The closely positive IGF-IR relationship was found between livers and sera (r = 0.91, t = 14.222, P < 0.01), respectively. CONCLUSION: IGF-IR expression may participate in rat hepatocarcinogenesis and its abnormality should be an early marker for hepatocytes malignant transformation.

AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated with CCl4 in rats for 84 d. Model was identified by measuring the ascetic amounts, hepatic function, portal pressure in vivo, splenic index, and pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84. After phenylephrine-induced constriction, Gly was geometrically used to reduce PHT. Gly action was expressed as median effective concentration (EC50) and area under the curve (AUC). Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and elevated portal pressure. Pathological findings had shown normal hepatic structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT rats. Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with PHT development, characterized with its EC50 at 2.80 × 10-10, 3.03 × 10-11, 3.77 × 10-11 and 4.65×10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS was located at hepatocyte at d0, stellate cells at d28, stellate cells and macrophages at d56, and macrophages in portal triads at d84. Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development. AUC values of Gly were positively correlated with existed iNOS levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma.Between April 2002 and July 2008, 220 hepatocellular carcinoma (HCC) patients who were diagnosed with HCC and underwent liver transplantation (LT) at our liver transplantation center were included. These patients were divided into three groups according to the characteristics of their tumors (tumor diameter, tumor number): the Milan criteria group (Group 1), the in up-to-seven group (Group 2) and the out up-to-seven group (Group 3). Then, we compared long-term survival and tumor recurrence of these three groups.The baseline characteristics of transplant recipients were comparable among these three groups, except for the type of liver graft (deceased donor liver transplant or live donor liver transplantation). There were also no significant differences in the pre-operative α-fetoprotein level. The 1-, 3-, and 5-year overall survival and tumor-free survival rate for the Milan criteria group were 94.8%, 91.4%, 89.7% and 91.4%, 86.2%, and 86.2% respectively; in the up-to-seven criteria group, these rates were 87.8%, 77.8%, and 76.6% and 85.6%, 75.6%, and 75.6% respectively (P0.05). However, the advanced HCC patients' (in the group out of up-to-seven criteria) overall and tumor-free survival rates were much lower, at 75%, 53.3%, and 50% and 65.8%, 42.5%, and 41.7%, respectively (P0.01).Considering that patients in the up-to-seven criteria group exhibited a considerable but lower survival rate compared with the Milan criteria group, the up-to-seven criteria should be used carefully and selectively.

To assess a relationship between longitudinal changes in liver fat content and biochemical parameters in obese children after 1-year nutritional intervention.Forty-six obese children, 21 males and 25 females, aged 6-14 years, underwent metabolic measurements, liver ultrasonography (US) and chemical-shift magnetic resonance imaging (MRI) examinations at baseline and after 1-year nutritional intervention. A child was defined obese if her/his body mass index (BMI) was above the age- and sex-adjusted BMI Cole's curve passing through the cut-off of 30 kg/m(2) at 18 years. BMI Z scores were calculated and adjusted for age and gender by using the Cole's LMS-method and Italian reference data. Biochemistry included serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Abdominal US and chemical-shift MRI were performed according to a randomized sequence. The same radiologist performed US by a GE Logiq 9 (General Electric Healthcare Medical Systems, Milwaukee, WI, United States) using a 3.5-MHz convex array transducer. Liver echogenicity was evaluated independently on videotape by 3 radiologists unaware of the child and MRI outcomes, and a consensus was established. Another experienced radiologist, unaware of the child and US data, performed the abdominal chemical-shift MRI with a 1-t system NT-Intera (Philips Medical Systems, Best, The Netherlands) and a phased-array coil. Liver fat fraction (FF) on MRI was judged elevated when greater than 9%. A FF18% was considered expressing more severe cases of fatty liver according to Fishbein. A nutritional-behavioral intervention was recommended to promote a normocaloric balanced diet and active lifestyle based on the Italian guidelines for treatment of childhood obesity.Compared to baseline, at the end of intervention children showed lower intakes of energy (mean ± SD: 2549 ± 1238 Kcal vs 1770 ± 622 Kcal, P0.0001), total fat (90 ± 47 g vs 52 ± 23 g, P0.0001), carbohydrates (356 ± 174 g vs 241 ± 111 g, P = 0.001), and protein (99 ± 48 g vs 75 ± 23 g, P = 0.006) intakes. Prevalence of FF ≥ 9% declined from 34.8% to 8.7% (P0.01), with a mean reduction of 7.8% (95%CI: 5.0-10.6). At baseline, FF was associated with liver biochemical parameters (maximum P0.001). At the end of the intervention association was found with AST (P = 0.017). Change of FF was associated with change in AST (P = 0.027) and ALT (P = 0.024). Rate of increased liver echogenicity declined from 45.6% to 21.7% (P0.0001). Liver echogenicity was associated with ALT at baseline only (P0.001). An age- and sex- adjusted multiple regression analysis showed that FF change was independently associated with change in serum AST (adjusted regression coefficient 0.348, P = 0.048).The results suggest that in obese children longitudinal changes in liver fat content based on MRI may be associated with change in serum transaminases suggesting novelty in monitoring nonalcoholic fatty liver disease.

To investigate the neuroprotective potential of ciclosporin during acute liver failure. We evaluated the effect of intrathecally administered ciclosporin on intracranial pressure, brain water content and aquaporin-4 expression in a rat model with acute hyperammonaemia.Twenty-four male Wistar rats with portacaval anastomosis were randomised into four groups receiving ciclosporin or vehicle and ammonia or saline infusion. Ciclosporin or vehicle was given intrathecally prior to the ammonia or saline infusion. The ammonia or saline infusion was given intravenously for 4 h, while intracranial pressure and arterial pressure was recorded. At the end of the experiment, cerebral cortex and cerebellar brain tissue was analysed for water and aquaporin-4 content.The following intracranial pressures were found at the end of the experiment: ammonia + ciclosporin: 10.0 ± 1.7 mmHg, ammonia + vehicle: 6.8 ± 1.0 mmHg, saline + ciclosporin: 3.1 ± 0.5 mmHg, saline + vehicle: 3.3 ± 0.6 mmHg. Ammonia infusion had a significant effect on intracranial pressure and brain water content, which both were higher in the groups receiving ammonia (P0.001, two-way analysis of variance). Treatment with ciclosporin resulted in relevant tissue concentrations of ciclosporin (0.2 micromolar) but did not reduce intracranial pressure after 4 h. Furthermore, ciclosporin did not attenuate the increase in cerebral water content, and did not affect aquaporin-4 expression.Intrathecal administration of ciclosporin does not attenuate intracranial hypertension or brain oedema in rats with portacaval anastomosis and 4 h of ammonia infusion.

To explore risk factors of lymphatic metastasis (LM) in gallbladder cancer, and their potential to complement unsatisfactory radiological detection.Radiological detection of LM by computed tomography (CT) was reported to fail in more than 60% of patients with pathological LM. In order to find risk factors highly suggestive of LM other than radiological manifestations, the documents of 63 patients were analyzed statistically. Except for 4 patients having T1a disease, in whom cholecystectomy is enough for radical resection, 59 patients underwent lymphadenectomy with at least 3 lymph nodes dissected. Fifty point eight percent (32/63) of patients were found to have LM during pathological examination. The median number of dissected lymph nodes was 6 (range 3-20).Only 31.3% (10/32) of patients with LM were detected by CT. Through multivariate analysis, two risk factors of LM were discovered as age60 years (OR = 6.24; P0.01) and carbohydrate antigen (CA) 19-9 elevation (OR = 5.70; P0.05). By analysis of patients with pathological LM but failed to be detected by CT, 81.8% (18/22) of patients had at least one risk factor, including 31.3% (10/32) who had the risk factor of age60 years, and 37.5% (12/32) who had the risk factor of CA 19-9 elevation. Besides, among patients with LM (n = 32), those whose age were younger than 60 years (OR = 3.41; P0.05) were more likely to have 3 or more positive lymph nodes.Age60 years and CA 19-9 elevation could complement radiological detection of LM. Patients aged60 years are at higher risk of multiple positive nodes.

AIM: To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process. METHODS: Twenty male patients undergoing subtotal gastrectomy were enrolled in this study. Young and elderly patient groups aged 25-40 years and 60-85 years, respectively, were included. Inclusion criteria were: no clinical evidence of cardiovascular, renal or diabetic diseases. Conventional clinical examinations were carried out. After surgery, gastric submucosal arteries were immediately dissected free of fat and connective tissue. Vascular responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured by isolated vascular perfusion. Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin (HE) staining and Verhoeff van Gieson (EVG) staining. The expression of xanthine oxidase (XO) and manganese-superoxide dismutase (Mn-SOD) was assessed by Western blotting analysis. The malondialdehyde (MDA) and hydrogen peroxide (H2O2) content and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined according to commercial kits. RESULTS: The overall structure of vessel walls was shown by HE and EVG staining, respectively. Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients; however, cell layer number in the vessel wall increased significantly in the elderly group. Compared with submucosal arteries in young patients, the amount of vascular collagen fibers, lumen diameter and media cross-sectional area were significantly increased in elderly patients. Ach- and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients. Compared with the young group, the expression of XO and the contents of MDA and H2O2 in gastric submucosal arterioles were increased in the elderly group. In addition, the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group. CONCLUSION: Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process.

AIM: To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS: This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its severity in each of 6 segments when endoscopic appearance is normal. Two subgroups of patients were compared: group 1 patients who developed CC/HGD and group 2 patients who did not develop CC/HGD. RESULTS: Of 115 patients with longstanding UC reviewed, 68 patients met the inclusion criteria. Twenty patients were in group 1 and 48 in group 2. We identified the number of times for each patient when the endoscopic appearance was normal but biopsies nevertheless showed inflammation. Overall, histological disease activity in the absence of gross/endoscopic disease was found in 31.2% (95%CI: 28%-35%) of colonoscopies performed on the entire cohort of 68 patients. Histological disease activity when the colonoscopy showed an absence of gross disease activity was more common in group 1 than group 2 patients, 88% (95%CI: 72%-97%) vs 59% (95%CI: 53%-64%). Only 3/20 (15%) of patients in group 1 ever had a colonoscopy completely without demonstrated disease activity (i.e., no endoscopic or histological activity) as compared to 37/48 (77%) of patients in group 2, and only 3.3% (95%CI: 0.09%-8.3%) of colonoscopies in group 1 had no histological inflammation compared to 23% (95%CI: 20%-27%) in group 2. CONCLUSION: Progression to HGD or CC in extensive ulcerative colitis of long standing was more frequently encountered among those patients who demonstrate persistent histological inflammation in the absence of gross mucosal disease. Our findings support including the elimination of histological inflammation in the definition of mucosal healing, and support this endpoint as an appropriate goal of therapy because of its risk of increasing dysplasia and colon cancer.

To investigate whether erosive esophagitis is correlated with metabolic syndrome and its components, abnormal liver function, and lipoprotein profiles.We conducted a cross-sectional, case control study of subjects who underwent upper endoscopy during a health examination at the Health Management and Evaluation Center of a tertiary medical care facility located in Southern Taiwan. Metabolic syndrome components, body mass index (BMI), liver function, dyslipidemia, and cardiovascular risk factors, as defined by the ratio of total cholesterol to high-density lipoprotein cholesterol (HDL-C), and the ratio of low-density lipoprotein cholesterol to HDL-C were compared between individuals with and without erosive esophagitis. Risk factors for erosive esophagitis were evaluated by multivariate logistic regression.Erosive esophagitis was diagnosed in 507 of 5015 subjects who were individually age and sex matched to 507 esophagitis-free control subjects. In patients with erosive esophagitis, BMI, waist circumference, blood pressure, fasting plasma glucose, triglyceride levels, aspartate aminotransferase, alanine aminotransferase, the ratio of total cholesterol to HDL-C, and the ratio of low-density lipoprotein cholesterol to HDL-C were significantly higher and HDL-C was significantly lower compared to patients without erosive esophagitis (all P0.05). In a multivariate analysis, central obesity (OR = 1.38; 95%CI: 1.0-1.86), hypertension (OR = 1.35; 95%CI: 1.04-1.76), hypertriglyceridemia (OR = 1.34; 95%CI: 1.02-1.76), cardiovascular risk factors as defined by a ratio of total cholesterol to HDL-C5 (OR = 1.45; 95%CI: 1.06-1.97), and aspartate aminotransferase (OR = 1.59; 95%CI: 1.08-2.34) were significantly associated with erosive esophagitis.Metabolic syndrome, impaired liver function, and a higher ratio of total cholesterol to HDL-C were associated with erosive esophagitis.

AIM: To investigate the effects of hypertonic saline in the neurocritical care population. METHODS: We retrospectively reviewed our hospital’s use of hypertonic saline (HS) since March of 2005, and prospectively since October 2010. Comparisons were made between admission diagnoses, creatinine change (Cr), and HS formulation (3% NaCl, 3% NaCl/sodium acetate mix, and 23.4% NaCl) to patients receiving normal saline or lactated ringers. The patients (n = 1329) of the retrospective portion were identified. The data presented represents the first 230 patients with data. RESULTS: Significant differences in Acute Physiology and Chronic Health Evaluation II scores and Glasgow Coma Scale scores occurred between different saline formulations. No significant correlation of Cl- or Na+ with Cr, nor with saline types, occurred. When dichotomized by diagnosis, significant correlations appear. Traumatic brain injury (TBI) patients demonstrated moderate correlation between Na+ and Cr of 0.45. Stroke patients demonstrated weak correlations between Na+ and Cr, and Cl- and Cr (0.19 for both). Patients receiving HS and not diagnosed with intracerebral hemorrhage, stroke, subarachnoid hemorrhage, or TBI demonstrated a weak but significant correlation between Cl- and Cr at 0.29. CONCLUSION: Cr directly correlates with Na+ or Cl- in stroke, Na+ in TBI, and Cl- in other populations. Prospective comparison of HS and renal function is needed.

AIM: To investigate time-dependent changes caused by temporal portal vein obstruction and subsequent reperfusion in the lobe with or without an occluded portal vein. METHODS: The portal vein (PV) of the anterior lobe of the liver of a male Wistar rat (8 wk-old) was obstructed (70%) for 12, 24, 36 and 48 h, respectively, and models were sacrificed at 48 h after reperfusion (each group: n = 10). The histological changes and the status of liver regeneration were compared between a liver biopsy performed on each lobe after temporary obstruction of the portal vein in the same rat liver, and the liver extracted at the time of sacrifice (48 h after reperfusion). RESULTS: With regard to the obstructed lobe, the liver weight/body weight ratio significantly decreased according to obstruction time. On the other hand, in the non-obstructed lobe, there were no significant differences within each group. The duration of PV occlusion did not seem to be strong enough to introduce liver weight increase. Stimulation of liver regeneration was brought about in the non-occluded lobe by 12-h occlusion, and was sustained even at 48 h after reperfusion. The obstructed lobe atrophied with the passage of time in the obstructed state. However, the proliferating-cell nuclear antigen labeling index also increased at 48 h after reperfusion, and a repair mechanism was observed. CONCLUSION: Temporary blood flow obstruction of the portal vein may become a significant trigger for liver regeneration, even with an obstruction of 12 h., World Journal of Gastroenterology, 19(34), pp.5700-5705; 2013

To study the diagnostic value of immunoglobulin heavy chain (IgH) and T-cell receptor γ (TCR-γ) gene monoclonal rearrangements in primary gastric lymphoma (PGL).A total of 48 patients with suspected PGL at our hospital were prospectively enrolled in this study from January 2009 to December 2011. The patients were divided into three groups (a PGL group, a gastric linitis plastica group, and a benign gastric ulcer group) based on the pathological results (gastric mucosal specimens obtained by endoscopy or surgery) and follow-up. Endoscopic ultrasonography (EUS) and EUS-guided biopsy were performed in all the patients. The tissue specimens were used for histopathological examination and for IgH and TCR-γ gene rearrangement polymerase chain reaction analyses.EUS and EUS-guided biopsy were successfully performed in all 48 patients. In the PGL group (n = 21), monoclonal IgH gene rearrangements were detected in 14 (66.7%) patients. A positive result for each set of primers was found in 12 (57.1%), 8 (38.1%), and 4 (19.0%) cases using FR1/JH, FR2/JH, and FR3/JH primers, respectively. Overall, 12 (75%) patients with mucosal-associated lymphoid tissue lymphoma (n = 16) and 2 (40%) patients with diffuse large B-cell lymphoma (n = 5) were positive for monoclonal IgH gene rearrangements. No patients in the gastric linitis plastica group (n = 17) and only one (10%) patient in the benign gastric ulcer group (n = 10) were positive for a monoclonal IgH gene rearrangement. No TCR-γ gene monoclonal rearrangements were detected. The sensitivity of monoclonal IgH gene rearrangements was 66.7% for a PGL diagnosis, and the specificity was 96.4%. In the PGL group, 8 (100%) patients with stage IIE PGL (n = 8) and 6 (46.1%) patients with stage IE PGL (n = 13) were positive for monoclonal IgH gene rearrangements.IgH gene rearrangements may be associated with PGL staging and may be useful for the diagnosis of PGL and for differentiating between PGL and gastric linitis plastica.

AIM: To investigate the diversity of Helicobacter pylori (H. pylori) genotypes and correlations with disease outcomes in an Iranian population with different gastroduodenal disorders. METHODS: Isolates of H. pylori from patients with different gastroduodenal disorders were analyzed after culture and identification by phenotypic and genotypic methods. Genomic DNA was extracted with the QIAamp DNA mini kit (Qiagen, Germany). After DNA extraction, genotyping was done for cagA, vacA (s and m regions), iceA (iceA1, iceA2) and babA with specific primers for each allele using polymerase chain reaction (PCR). All patients’ pathologic and clinical data and their relation with known genotypes were analyzed by using SPSS version 19.0 software. χ2 test and Fisher’s exact test were used to assess relationships between categorical variables. The level of statistical significance was set at P < 0.05. RESULTS: A total of 71 isolates from 177 patients with different gastroduodenal disorders were obtained. Based on analysis of the cagA gene (positive or negative), vacA s-region (s1 or s2), vacA m-region (m1 or m2), iceA allelic type (iceA1 and iceA2) and babA gene (positive or negative), twenty different genotypic combinations were recognized. The prevalence of cagA, vacA s1, vacA s2, vacA m1, vacA m2, iceA1, iceA2, iceA1+iceA2 and babA were 62%, 78.9%, 19.7%, 21.1%, 78.9%, 15.5%, 22.5%, 40.8% and 95.8%, respectively. Interestingly, evaluation of PCR results for cagA in 6 patients showed simultaneous existence of cagA variants according to their size diversities that proposed mixed infection in these patients. The most prevalent genotype in cagA-positive isolates was cagA+/vacAs1m2/iceA1+A2/babA+ and in cagA-negative isolates was cagA-/vacAs1m2/iceA-/babA+. There were no relationships between the studied genes and histopathological findings (H. pylori density, neutrophil activity, lymphoid aggregation in lamina propria and glandular atrophy). The strains which carry cagA, vacAs1/m1, iceA2 and babA genes showed significant associations with severe active chronic gastritis (P = 0.011, 0.025, 0.020 and 0.031, respectively). The vacAs1 genotype had significant correlation with the presence of the cagA gene (P = 0.013). Also, babA genotype showed associations with cagA (P = 0.024). In the combined genotypes, only cagA+/vacAs1m1/iceA2/babA+ genotype showed correlation with severe active chronic gastritis (P = 0.025). CONCLUSION: This genotyping panel can be a useful tool for detection of virulent H. pylori isolates and can provide valuable guidance for prediction of the clinical outcomes.

AIM: To evaluate if 3 mo oral supplementation with Eviendep® was able to reduce the number of duodenal polyps in familial adenomatous polyposis (FAP) patients with ileal pouch-anal anastomosis (IPAA). METHODS: Eleven FAP patients with IPAA and duodenal polyps were enrolled. They underwent upper gastrointestinal (GI) endoscopy at the baseline and after 3 mo of treatment. Each patient received 5 mg Eviendep twice a day, at breakfast and dinner time, for 3 mo. Two endoscopists evaluated in a blinded manner the number and size of duodenal polyps. Upper GI endoscopies with biopsies were performed at the baseline (T0) with the assessment of the Spigelman score. Polyps > 10 mm were removed during endoscopy and at the end of the procedure a new Spigelman score was determined (T1). The procedure was repeated 3 mo after the baseline (T2). Four photograms were examined for each patient, at T1 and T2. The examined area was divided into 3 segments: duodenal bulb, second and third portion duodenum. Biopsy specimens were taken from all polyps > 10 mm and from all suspicious ones, defined by the presence of a central depression, irregular surface, or irregular vascular pattern. Histology was classified according to the updated Vienna criteria. RESULTS: At baseline the mean number of duodenal detected polyps was 27.7 and mean sizes were 15.8 mm; the mean Spigelman score was 7.1. After polypectomy the mean number of duodenal detected polyps was 25.7 and mean sizes were 7.6 mm; the mean Spigelman score was 6.4. After 3 mo of Eviendep bid, all patients showed a reduction of number and size of duodenal polyps. The mean number of duodenal polyps was 8 (P = 0.021) and mean size was 4.4 mm; the mean Spigelman score was 6.6. Interrater agreement was measured. Lesions > 1 cm found a very good degree of concordance (kappa 0.851) and a good concordance was as well encountered for smaller lesions (kappa 0.641). CONCLUSION: Our study demonstrated that short-term (90 d) supplementation with Eviendep® in FAP patients with IPAA and with recurrent adenomas in the duodenal mucosa, resulted effective in reducing polyps number of 32% and size of 51%.

AIM: To study the natural history, patterns and clinical characteristics of inflammatory bowel diseases (IBD) in Egypt. METHODS: We designed a case-series study in the gastroenterology centre of the Internal Medicine department of Cairo University, which is a tertiary care referral centre in Egypt. We included all patients in whom the diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) was confirmed by clinical, laboratory, endoscopic, histological and/or radiological criteria over the 15 year period from 1995 to 2009, and we studied their sociodemographic and clinical characteristics. Endoscopic examinations were performed by 2 senior experts. This hospital centre serves patients from Cairo, as well as patients referred from all other parts of Egypt. Our centre received 24156 patients over the described time period for gastro-intestinal consultations and/or interventions. RESULTS: A total of 157 patients with established IBD were included in this study. Of these, 135 patients were diagnosed with UC (86% of the total), and 22 patients, with CD (14% of the total). The mean ages at diagnosis were 27.3 and 29.7, respectively. Strikingly, we noticed a marked increase in the frequency of both UC and CD diagnoses during the most recent 10 years of the 15 year period studied. Regarding the gender distribution, the male:female ratio was 1:1.15 for UC and 2.6:1 for CD. The mean duration of follow up for patients with UC was 6.2 ± 5.18 years, while the mean duration of follow up for patients with CD was 5.52 ± 2.83 years. For patients with UC we found no correlation between the severity of the disease and the presence of extraintestinal manifestations. Eleven patients had surgical interventions during the studied years: 4 cases of total colectomy and 7 cases of anal surgery. CONCLUSION: We observed a ratio of 6:1 for UC to CD in our series. The incidence of IBD seems to be rising in Egypt.

AIM: To investigate the potential role of khat in triggering auto immune hepatitis. METHODS: Patients with a history of khat use and acute hepatitis were identified using the computer database in the hepatology department at the Royal Hallamshire Hospital. They were then assessed for probability of having autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria. RESULTS: Six patients were identified. All of them had presented with acute hepatitis on a background of khat. All were male and five of these patients were of Somali origin, while one patient was from Yemen. The patients were given points on the modified autoimmune hepatitis score which is based on their liver enzymes, autoimmune screen, exclusion of viral hepatitis alcohol and drugs, immunoglobulin levels and liver histology. The patients were given a score of -4 for khat use due to its potential to cause drug induced liver injury. Five of these patients scored between 10 and 15 points, placing them in the probable group for having autoimmune hepatitis. All of these patients were treated with prednisolone and demonstrated a good response to immunosuppression. CONCLUSION: One possibile cause of hepatotoxicity with khat could be via triggering of autoimmune hepatitis in a genetically susceptible individual. Further studies are needed for confirmation.

AIM: To validate the “Metroticket” predictor using a large cohort of liver transplantation (LT) patients with hepatocellular carcinoma (HCC) in China. METHODS: In total, 230 cases of LT for HCC treatment at our center, from July 2000 to August 2008, were included in the present study. The predicted 1-, 3- and 5-year post-LT survival rates were calculated using the Metroticket model (http://89.96.76.14/metroticket/calculator/). The predicted and observed long-term survival rates were then compared and analyzed. RESULTS: The predicted survival rates for all 230 cases, as calculated by the Metroticket model, were 64.7% and 56.2% at 3 and 5 years, respectively, and the observed survival rates for these patients were 71.3% and 57.8%, respectively. For the 23 cases with macrovascular invasion, the predicted 5-year survival rate was 43.5%, whereas the observed 5-year survival rate was only 8.7%. For the 42 cases with microvascular invasion but an absence of macrovascular invasion, the predicted 5-year survival rate was 44.9%, and the observed 5-year survival rate was 50%. For the remaining 165 patients without any vascular invasion, the predicted 5-year survival rate was 65.8%, and the observed 5-year survival rate was 66.7%. CONCLUSION: The Metroticket model can be used to accurately predict survival in HCC-related LT cases with an absence of macrovascular invasion.

AIM: To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients. METHODS: Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software. RESULTS: The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 ± 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 ± 0.4, 6.6 ± 0.4, and 7.2 ± 0.4, respectively. The density of serotonin cells in the ileum was 40.6 ± 3.6 cells/mm2 in the controls, and 11.5 ± 1.2, 10.7 ± 5.6, 10.0 ± 1.9, and 13.9 ± 1.4 cells/mm2 in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P < 0.0001, P = 0.0001, P = 0.0001, and P < 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 ± 1.6 cells/mm2 in the controls, and 33.1 ± 1.4, 27.5 ± 1.4, 34.1 ± 2.5, and 41.7 ± 3.1 cells/mm2 in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and < 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells. CONCLUSION: The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients. publishedVersion

AIM: To evaluate the feasibility, safety, and effectiveness of consecutive laparoscopic cholecystectomy (LC) plus splenectomy (LS) in liver cirrhosis patients. METHODS: From 2003 to 2013, 17 (group 1) patients with liver cirrhosis complicated by hypersplenism and symptomatic gallstones were treated with combined LC and LS, while 58 (group 2) patients with liver cirrhosis and hypersplenism received LS alone. An additional 14 (group 3) patients who received traditional open procedures during the same period were included as controls. Data were retrospectively collected and reviewed in regard to demographic characteristics and preoperative, intraoperative and postoperative features. Differences between the three groups were assessed by statistical analysis. RESULTS: The three groups showed no significant differences in the demographic characteristics or preoperative status. However, the patients treated with LC and LS required significantly longer operative time, shorter postoperative stay as well as shorter time of return to the first oral intake, and suffered less intraoperative blood loss as well as fewer postoperative surgical infections than the patients treated with traditional open procedures (group 1 vs group 3, P < 0.05 for all). The patients treated with LC and LS showed no significant differences in the intraoperative and postoperative variables from those treated with LS alone (group 1 vs group 2). All patients showed significant improvements in the haematological responses (preoperative period vs postoperative period, P < 0.05 for all). None of the patients treated with LC and LS presented with any gallstone-associated symptoms following discharge, while the patients treated with the traditional open procedures expressed complaints of discomfort related to their surgical incisions. CONCLUSION: Consecutive LC and LS is an appropriate treatment option for liver cirrhosis patients with gallstones and hypersplenism, especially for those with Child-Pugh A and B.

To evaluate the expression of Bcl-xL, Bak, and Bax proteins in correlation with particular clinico-histopathological parameters, including tumor invasion front, in patients with colorectal cancer.The expression of these proteins was evaluated with the use of the immunohistochemical method in 50 primary tumors.According to observations, a low expression of Bax and Bak proteins is related to the localization of the tumor in the rectum (P0.05 and P0.05 respectively), which may explain an increased incidence of colorectal cancer in this area. A positive expression of Bax protein also correlates with the presence of cancer cell infiltration to lymph and blood vessels (P0.05), which may suggest the participation of this protein in the early stages of colorectal cancer progression. Moreover, a positive expression of Bcl-xL protein correlated with a positive expression of Bak protein. This may suggest a greater participation of Bcl-xL protein in the inhibition of the proapoptotic Bak protein, but not the Bax protein.Bax protein is probably very significant in the cancerogenesis mechanism in the large intestine.

To investigate H2O2-induced promotion proliferation and malignant transformation in WB-F344 cells and anti-tumor effects of ursolic acid (UA) and oleanolic acid (OA).WB-F344 cells were continuously exposed to 7 x 10(-7) mol/L H2O2 for 21 d. Observations of cell morphology, colony formation rates, flow cytometric analysis of cell cycle changes and aneuploidy formation indicated that H2O2 was able to induce malignant transformation of WB-F344 cells. We treated malignantly transformed WB-F344 cells with 4 μmol/L OA or 8 μmol/L UA for 72 h and analyzed the cell cycle distribution by flow cytometry.MTT assay showed that 7 x 10(-7) mol/L H2O2 decreased G1 phase subpopulation from 73.8% to 49.6% compared with the control group, and increased S phase subpopulation from 14.5% to 31.8% (P0.05 vs control group). Cell morphology showed that nucleus to cytoplasm ratio increased, many mitotic cells, prokaryotes and even tumor giant cells were shown in H2O2-induced WB-F344 cells. Fluorescence activated cell sorting analysis showed that WB-F344 cell aneuploidy increased to 12% following H2O2 treatment. Flow cytometric analysis of the transformed WB-F344 cells following treatment with OA (4 μmol/L) and UA (8 μmol/L) showed that OA increased G1 subpopulation to 68.6%, compared to 49.7% in unexposed cells. UA increased G1 subpopulation to 67.4% compared to 49.7% in unexposed cells (P0.05 vs H2O2 model group).H2O2 causes the malignant transformation of WB-F344 cells. OA and UA exert anti-tumor effects by inhibiting the proliferation in malignantly transformed WB-F344 cells.

To summarize our experience in the application of Crurasoft® for antireflux surgery and hiatal hernia (HH) repair and to introduce the work of Chinese doctors on this topic.Twenty-one patients underwent HH repair with Crurasoft® reinforcement. Gastroesophageal reflux disease (GERD) and HH-related symptoms including heartburn, regurgitation, chest pain, dysphagia, and abdominal pain were evaluated preoperatively and 6 mo postoperatively. A patient survey was conducted by phone by one of the authors. Patients were asked about "recurrent reflux or heartburn" and "dysphagia". An internet-based Chinese literature search in this field was also performed. Data extracted from each study included: number of patients treated, hernia size, hiatorrhaphy, antireflux surgery, follow-up period, recurrence rate, and complications (especially dysphagia).There were 8 type I, 10 type II and 3 type III HHs in this group. Mean operative time was 119.29 min (range 80-175 min). Intraoperatively, length and width of the hiatal orifice were measured, (4.33 ± 0.84 and 2.85 ± 0.85 cm, respectively). Thirteen and eight Nissen and Toupet fundoplications were performed, respectively. The intraoperative complication rate was 9.52%. Despite dysphagia, GERD-related symptoms improved significantly compared with those before surgery. The recurrence rate was 0% during the 6-mo follow-up period, and long-term follow-up disclosed a recurrence rate of 4.76% with a mean period of 16.28 mo. Eight patients developed new-onset dysphagia. The Chinese literature review identified 12 papers with 213 patients. The overall recurrence rate was 1.88%. There was no esophageal erosion and the rate of dysphagia ranged from 0% to 24%.The use of Crurasoft® mesh for HH repair results in satisfactory symptom control with a low recurrence rate. Postoperative dysphagia continues to be an issue, and requires more research to reduce its incidence.

To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis.Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected, from January 2002 to December 2006, were analyzed retrospectively. Patients with pT4 stage or distant metastasis were excluded. We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features, such as age, tumor size, tumor location and depth of invasion. At the same time, the relationship between postoperative chemotherapy and the 5-year survival rate among different subgroups were also analyzed.The overall 5-year survival rate of the entire cohort was 63.7%. The 5-year survival rate was poor in those patients who were: (1) more than 65 years old; (2) with tumor size larger than 4 cm; (3) with tumor located in the upper portion of the stomach; and (4) with pT3 tumor. The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor (P = 0.019), but not in other subgroups. Moreover, there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups (P0.05).For gastric cancer patients without lymph node metastasis, extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor. However, there was no evidence of a survival benefit from postoperative chemotherapy alone.