The Scientific World Journal: Gastroenterology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Corrigendum to “Low Body Mass Index Can Identify Majority of Osteoporotic Inflammatory Bowel Disease Patients Missed by Current Guidelines” Mon, 14 Aug 2017 00:00:00 +0000 Ashish Atreja, Ashish Aggarwal, Angelo A. Licata, and Bret A. Lashner Copyright © 2017 Ashish Atreja et al. All rights reserved. Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate Thu, 22 Dec 2016 07:56:28 +0000 In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes. Halyna M. Kuznietsova, Maryna S. Yena, Iryna P. Kotlyar, Olexandr V. Ogloblya, and Volodymyr K. Rybalchenko Copyright © 2016 Halyna M. Kuznietsova et al. All rights reserved. Excretory Function of Intestinal Tract Enhanced in Kidney Impaired Rats Caused by Adenine Tue, 15 Nov 2016 07:15:21 +0000 The main aim of the study was to prove the compensative effect of intestine for renal function. Rat kidney was impaired by intragastrically administrating adenine (400 mg per day for 5 days). Intestinal tract was harvested and equally divided into 20 segments except cecum. Kidneys were harvested and histologically examined with hematoxylin-eosin staining kits. Uric acid, urea (BUN), and creatinine in serum were determined with assay kits, and BUN and creatinine in every intestinal segment were also determined. The results showed that adenine was able to increase uric acid level in serum from  μg/mL to  μg/mL and cause renal function damage with BUN (from  mM to 12. mM) and creatinine (from μM to μM) increasing in serum and with abnormally micromorphological changes in kidney. The amount of BUN and creatinine distributed in intestinal tract was positively correlated with those in blood. In impaired renal function rats, the amount of BUN (from μMole to 10.μMole) and creatinine (from nMole to nMole) distributed in intestinal tract significantly increased. All the results proved that intestinal tract had excretory function compensative for renal function. Yu Yun, Tao Gao, Yue Li, Zhiyi Gao, Jinlian Duan, Hua Yin, and Weigang Duan Copyright © 2016 Yu Yun et al. All rights reserved. System Review about Function Role of ESCC Driver Gene KDM6A by Network Biology Approach Tue, 17 May 2016 06:07:52 +0000 Background. KDM6A (Lysine (K)-Specific Demethylase 6A) is the driver gene related to esophageal squamous cell carcinoma (ESCC). In order to provide more biological insights into KDM6A, in this paper, we treat PPI (protein-protein interaction) network derived from KDM6A as a conceptual framework and follow it to review its biological function. Method. We constructed a PPI network with Cytoscape software and performed clustering of network with Clust&See. Then, we evaluate the pathways, which are statistically involved in the network derived from KDM6A. Lastly, gene ontology analysis of clusters of genes in the network was conducted. Result. The network includes three clusters that consist of 74 nodes connected via 453 edges. Fifty-five pathways are statistically involved in the network and most of them are functionally related to the processes of cell cycle, gene expression, and carcinogenesis. The biology themes of clusters 1, 2, and 3 are chromatin modification, regulation of gene expression by transcription factor complex, and control of cell cycle, respectively. Conclusion. The PPI network presents a panoramic view which can facilitate for us to understand the function role of KDM6A. It is a helpful way by network approach to perform system review on a certain gene. Jihua Ran, Hui Li, and Huiwu Li Copyright © 2016 Jihua Ran et al. All rights reserved. Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma Mon, 14 Dec 2015 12:19:32 +0000 The development of esophageal squamous cell carcinoma (ESCC) is poorly understood and the major regulatory molecules involved in the process of tumorigenesis have not yet been identified. We had previously employed a quantitative proteomic approach to identify differentially expressed proteins in ESCC tumors. A total of 238 differentially expressed proteins were identified in that study including S100 calcium binding protein A9 (S100A9) as one of the major downregulated proteins. In the present study, we carried out immunohistochemical validation of S100A9 in a large cohort of ESCC patients to determine the expression and subcellular localization of S100A9 in tumors and adjacent normal esophageal epithelia. Downregulation of S100A9 was observed in 67% () of 288 different ESCC tumors, with the most dramatic downregulation observed in the poorly differentiated tumors (99/111). Expression of S100A9 was restricted to the prickle and functional layers of normal esophageal mucosa and localized predominantly in the cytoplasm and nucleus whereas virtually no expression was observed in the tumor and stromal cells. This suggests the important role that S100A9 plays in maintaining the differentiated state of epithelium and suggests that its downregulation may be associated with increased susceptibility to tumor formation. Harsh Pawar, Srinivas M. Srikanth, Manoj Kumar Kashyap, Gajanan Sathe, Sandip Chavan, Mukul Singal, H. C. Manju, Kariyanakatte Veeraiah Veerendra Kumar, M. Vijayakumar, Ravi Sirdeshmukh, Akhilesh Pandey, T. S. Keshava Prasad, Harsha Gowda, and Rekha V. Kumar Copyright © 2015 Harsh Pawar et al. All rights reserved. Ocular Complications of Inflammatory Bowel Disease Mon, 23 Mar 2015 11:16:24 +0000 Though inflammatory bowel disease (IBD) has a specific predilection for the intestinal tract, it is a systemic inflammatory disorder affecting multiple organs, including the eye. Ocular complications directly related to IBD are categorized as primary and secondary. Primary complications are usually temporally associated with IBD exacerbations and tend to resolve with systemic treatment of the intestinal inflammation. These include keratopathy, episcleritis, and scleritis. Secondary complications arise from primary complications. Examples include cataract formation due to treatment with corticosteroids, scleromalacia due to scleritis, and dry eye due to hypovitaminosis A following gut resection. Some ocular manifestations of IBD can lead to significant visual morbidity and temporally associated complications can also be a herald of disease control. Furthermore, ocular manifestations of IBD can occasionally manifest before the usual intestinal manifestations, leading to an earlier diagnosis. Thus, it is important to understand the clinical presentation of possible ocular manifestations in order to initiate appropriate treatment and to help prevent significant visual morbidity. Rana Mady, Will Grover, and Salim Butrus Copyright © 2015 Rana Mady et al. All rights reserved. Royal Jelly and Its Dual Role in TNBS Colitis in Mice Mon, 02 Mar 2015 07:51:41 +0000 Royal Jelly (RJ) is widely consumed in diets throughout the world due to its beneficial effects: antioxidant, antitumor and anti-inflammatory. We have investigated the role of RJ in the development of TNBS colitis in mice. Colitis was induced by a rectal instillation of TNBS at 0.1 mL per mouse. Intestine samples of the animals orally treated with RJ (100, 150, and 200 mg/kg) were collected for antioxidant assays (GSH and GSH-Px), proinflammatory protein quantification (COX-2 and NF-κB), and histological analyses. RJ 100 mg/kg maintained GSH levels and increased the activity of GSH-Px, downregulated key inflammatory mediators (COX-2 and NF-κB), and decreased the lesions caused by TNBS as shown by the histological analyses. In conclusion, RJ showed anti-inflammatory and antioxidant properties in experimental colitis, resulting in the amelioration of the macroscopic and histological analyses. These results corroborate with the RJ supplementation in diets. Luis Paulo Manzo, Felipe Meira de-Faria, Ricardo José Dunder, Eduardo Augusto Rabelo-Socca, Silvio Roberto Consonni, Ana Cristina Alves de Almeida, Alba Regina Monteiro Souza-Brito, and Anderson Luiz-Ferreira Copyright © 2015 Luis Paulo Manzo et al. All rights reserved. Low Molecular Weight Heparin in Portal Vein Thrombosis of Cirrhotic Patients: Only Therapeutic Purposes? Mon, 29 Dec 2014 06:46:39 +0000 Cirrhosis has always been regarded as hemorrhagic coagulopathy caused by the reduction in the hepatic synthesis of procoagulant proteins. However, with the progression of liver disease, the cirrhotic patient undergoes a high rate of thrombotic phenomena in the portal venous system. Although the progression of liver failure produces a reduction in the synthesis of anticoagulant molecules, a test able to detect the patients with hemostatic balance shifting towards hypercoagulability has not yet been elaborated. The need of treatment and/or prophylaxis of cirrhotic patients is demonstrated by the increased mortality, the risk of bleeding from esophageal varices, and the mortality of liver transplantation, when portal vein thrombosis (PVT) occurs even if current guidelines do not give indications about PVT treatment in cirrhosis. In view of the general feeling that the majority of cirrhotic patients at an advanced stage may be in a procoagulant condition (suggested by the sharp increase in the prevalence of PVT), it is presumable that a prophylaxis of this population could be of benefit. The safety and the efficacy of prophylaxis and treatment with enoxaparin in patients with cirrhosis demonstrated by a single paper suggest this option only in controlled trials and, currently, there are no sufficient evidences for a recommendation in the clinical practice. Raffaele Licinio, Mariabeatrice Principi, Giuseppe Losurdo, Nicola Maurizio Castellaneta, Enzo Ierardi, and Alfredo Di Leo Copyright © 2014 Raffaele Licinio et al. All rights reserved. Helicobacter pylori Infection and Insulin Resistance in Diabetic and Nondiabetic Population Thu, 23 Oct 2014 00:00:00 +0000 Helicobacter pylori (HP) is a common worldwide infection with known gastrointestinal and nongastrointestinal complications. One of the gastrointestinal side effects posed for this organism is its role in diabetes and increased insulin resistance. The aim of this study was to evaluate the association between HP and insulin resistance in type 2 diabetic patients and nondiabetics. This cross-sectional study was carried out from May to December 2013 on 211 diabetic patients referred to diabetes clinic of Shahid Beheshti Hospital of Qom and 218 patients without diabetes. HP was evaluated using serology method and insulin resistance was calculated using HOMA-IR. The prevalence of H. pylori infection was 55.8% and 44.2% in diabetics and nondiabetics . The study population was divided into two HP positive and negative groups. Among nondiabetics, insulin resistance degree was and in HP+ and HP− patients, respectively . Oppositely, insulin resistance was significantly higher in diabetic HP+ patients rather than seronegative ones versus , . In diabetic patients, in addition to higher prevalence of HP, it causes a higher degree of insulin resistance. Jamshid Vafaeimanesh, Mahmoud Parham, Mohammadreza Seyyedmajidi, and Mohammad Bagherzadeh Copyright © 2014 Jamshid Vafaeimanesh et al. All rights reserved. Bone Mineral Density at Diagnosis of Celiac Disease and after 1 Year of Gluten-Free Diet Tue, 14 Oct 2014 08:40:04 +0000 Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <−1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients. Stefano Pantaleoni, Massimo Luchino, Alessandro Adriani, Rinaldo Pellicano, Davide Stradella, Davide Giuseppe Ribaldone, Nicoletta Sapone, Gian Carlo Isaia, Marco Di Stefano, and Marco Astegiano Copyright © 2014 Stefano Pantaleoni et al. All rights reserved. Myotubularin-Related Phosphatase 3 Promotes Growth of Colorectal Cancer Cells Tue, 19 Aug 2014 06:00:16 +0000 Due to changes in lifestyle, particularly changes in dietary habits, colorectal cancer (CRC) increased in recent years despite advances in treatment. Nearly one million new cases diagnosed worldwide and half a million deaths make CRC a leading cause of cancer mortality. In the present study, we aimed to investigate the role of myotubularin-related phosphatase 3 (MTMR3) in CRC cell growth via lentivirus-mediated small interfering RNA (siRNA) transduction in human colon cancer cell lines HCT116 and SW1116. The effect of MTMR3 knockdown on cell growth was evaluated by MTT, colony formation, and flow cytometry assays. The effect of MTMR3 knockdown on cell apoptosis was evaluated by flow cytometry with Annexin V/7-AAD double staining. The activation of apoptotic markers, Bad and PARP, was detected using Intracellular Signaling Array. Knockdown of MTMR3 resulted in a significant reduction in cell proliferation in both HCT116 and SW1116 cells. Moreover, knockdown of MTMR3 led to S phase cell cycle arrest. Furthermore, knockdown of MTMR3 induced cell apoptosis via phosphorylation of Bad and cleavage of PARP. These results indicate that MTMR3 may play an important role in the progression of CRC and suggest that siRNA mediated silencing of MTMR3 could be an effective tool in CRC treatment. Bo’an Zheng, Xiaojun Yu, and Rui Chai Copyright © 2014 Bo’an Zheng et al. All rights reserved. Efficacy and Safety of Acotiamide for the Treatment of Functional Dyspepsia: Systematic Review and Meta-Analysis Tue, 12 Aug 2014 09:17:16 +0000 Background. There are no treatments with established efficacy for this disorder so far. Aim. To systematically review the efficacy of acotiamide in the treatment of patients with FD. Methods. We searched main electronic databases through November 2013. RCTs evaluating the efficacy of acotiamide versus placebo in FD patients were included. Pooled risk ratio (RR) with 95% confidential interval (CI) was calculated. Results. Six publications including seven RCTs were eligible for inclusion. The summary RR of overall improvement of FD symptoms in patients receiving acotiamide versus placebo was 1.29 (95% CI, 1.19–1.40, ; %). Acotiamide improved the symptoms of patients with postprandial distress syndrome (PDS) (RR, 1.29; 95% CI, 1.09–1.53, ; %), and the summary RR for patients with epigastric pain syndrome (EPS) was 0.92 (95% CI, 0.76–1.11, ; %). Acotiamide showed a significantly beneficial effect on the elimination of some individual FD symptoms compared with placebo. Adverse events were not significantly different between acotiamide and placebo groups. Subgroup analyses suggested that acotiamide 100 mg three times daily (tid) showed consistent efficacy not only for the overall improvement but also for the elimination of some individual symptoms in FD patients. Conclusions. Acotiamide has the potential to improve the symptoms of patients with FD, particularly of patients with PDS, without major adverse effects. The dosage of acotiamide 100 mg tid might be the appropriate dose in the treatment of FD. Guoguang Xiao, Xiaoping Xie, Juan Fan, Jianjun Deng, Shan Tan, Yu Zhu, Qin Guo, and Chaomin Wan Copyright © 2014 Guoguang Xiao et al. All rights reserved. Gastroprotective Activity of Violacein Isolated from Chromobacterium violaceum on Indomethacin-Induced Gastric Lesions in Rats: Investigation of Potential Mechanisms of Action Tue, 05 Aug 2014 08:47:21 +0000 Chromobacterium violaceum, Gram-negative bacteria species found in tropical regions of the world, produces a distinct deep violet-colored pigment called violacein. In the present study, we investigated whether violacein can promote a gastroprotective effect and verified the possible mechanisms involved in this action. For this study, an indomethacin-induced gastric ulcer rat model was used. The roles of biomolecules such as MPO, PGE2, pro- and anti-inflammatory cytokines, growth factors, caspase-3, NO, K+ATP channels, and α2-receptors were investigated. Violacein exhibited significant gastroprotective effect against indomethacin-induced lesions, while pretreatment with L-NAME and glibenclamide (but not with NEM or yohimbine) was able to reverse this action. Pretreatment with violacein also restored cNOS level to normal and led to attenuation of enhanced apoptosis and gastric microvascular permeability. Our results suggest that violacein provides a significant gastroprotective effect in an indomethacin-induced ulcer model through the maintenance of some vital protein molecules, and this effect appears to be mediated, at least in part, by endogenous prostaglandins, NOS, K+ATP channel opening, and inhibition of apoptosis and gastric microvascular permeability. Paulrayer Antonisamy, Ponnusamy Kannan, Adithan Aravinthan, Veeramuthu Duraipandiyan, Mariadhas Valan Arasu, Savarimuthu Ignacimuthu, Naif Abdullah Al-Dhabi, and Jong-Hoon Kim Copyright © 2014 Paulrayer Antonisamy et al. All rights reserved. Can Vascular Endothelial Growth Factor and Microvessel Density Be Used as Prognostic Biomarkers for Colorectal Cancer? A Systematic Review and Meta-Analysis Thu, 27 Mar 2014 14:18:07 +0000 Background. Vascular endothelial growth factor (VEGF) and microvessel density (MVD) are associated with greater incidence of metastases and decreased survival. Whether they can be used as prognostic indicators of colorectal cancer (CRC) is still controversial. Methods. The authors performed a meta-analysis using the results of a literature search of databases of PubMed and EMBASE, and the references of articles included in the analysis. Meta-analysis was performed using random effects model and hazard ratios (HRs) and 95% confidence intervals (CIs) as effect measures. Results. Twenty studies contributed to the analysis of VEGF, of which 16 were used for overall survival (OS) and 9 for disease-free survival (DFS). High VEGF levels has a relationship with unfavorable survival (OS: HR = 1.98, 95% CI: 1.30–3.02; DFS: HR = 2.10, 95% CI: 1.26–3.49) and a 4.22-fold increase in the rate of distant metastases. Analysis was performed on 18 studies for MVD; the results showed that patients with high MVD expression in tumors appeared to have poorer overall survival (HR = 1.39, 95% CI: 1.22–1.58) and were at a greater risk of having unfavorable clinical characteristics related to prognosis. Corresponding results were obtained from quantitative and/or qualitative analysis of clinicopathological. Conclusions. The meta-analysis demonstrates that VEGF and MVD can be used as prognostic biomarkers for CRC patients. Yibaina Wang, Xiaoping Yao, Jie Ge, Fulan Hu, and Yashuang Zhao Copyright © 2014 Yibaina Wang et al. All rights reserved. Y-Shaped Bilateral Self-Expandable Metallic Stent Placement for Malignant Hilar Biliary Obstruction: Data from a Referral Center for Palliative Care Sun, 23 Mar 2014 11:45:59 +0000 Background and Aim. Malignant hilar strictures are a clinical challenge because of the current therapeutic approach and the poor prognosis. In recent years, self-expandable metallic stents have proven more effective than plastic stents for palliation of malignant hilar strictures, with the bilateral stent-in-stent technique registering a high success rate. We report our experience with Y-shaped endoscopic self-expandable metallic stents placement for treatment of advanced malignant hilar strictures. Methods. From April 2009 to August 2012, we prospectively collected data on patients treated with Y-shaped SEMS placement for advanced malignant hilar carcinoma. Data on technical success, clinical success, and complications were collected. Results. Twenty patients (9 males) were treated (mean age 64.2 ± 15.3 years). The grade of malignant hilar strictures according to the Bismuth classification was II in 5 patients (25%), IIIa in 1 (5%), and IV in 14 (70%). The mean bilirubin level was 14.7 ± 4.9 mg/dL. Technical success was achieved in all patients, with a significant reduction in bilirubin levels (2.9 ± 1.7 mg/dL). One patient experienced cholangitis as early complication, while in 2 patients stent ingrowth was observed. No stents migration was recorded. There was no procedure-related mortality. At the end of the follow-up (7.1 ± 3.1 months), 13 of the 20 patients (65%) had died. Conclusions. Our experience confirms endoscopic bilateral self-expandable metallic stents placement with stent-in-stent technique (Y-shaped configuration) as a feasible, effective, and safe procedure for palliation of unresectable malignant hilar strictures. R. Di Mitri and F. Mocciaro Copyright © 2014 R. Di Mitri and F. Mocciaro. All rights reserved. Effect of Monotherapy and Combination Therapy of Pantoprazole and Aprepitant in Gastric Esophageal Reflux Disease in Albino Rats Sun, 23 Mar 2014 09:23:41 +0000 The present study was undertaken to elucidate the effect of pantoprazole and aprepitant on experimental esophagitis in albino rats. Groups of rats, fasted overnight, received normal saline (3 mL/kg, sham control) or toxic control (3 mL/kg) or pantoprazole (30 mg/kg) or aprepitant (10 mg/kg), or their combinations and were subjected to pylorus and forestomach ligation. Animals were sacrificed after 8 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index, and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with pantoprazole and aprepitant significantly inhibited the gastric secretion, total acidity, and esophagitis index. The treatment also helped to restore the altered levels oxidative stress parameters to normal. Kamleshwar Shukla, Prince Raj, Arun Kumar, Mukesh Kumar, and Gaurav Kaithwas Copyright © 2014 Kamleshwar Shukla et al. All rights reserved. Expression Profiling Using a cDNA Array and Immunohistochemistry for the Extracellular Matrix Genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in Colorectal Carcinoma Progression and Dissemination Tue, 04 Mar 2014 11:16:30 +0000 Colorectal cancer dissemination depends on extracellular matrix genes related to remodeling and degradation of the matrix structure. This investigation intended to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene and protein expression levels in tumor tissue with clinical and histopathological neoplastic parameters of cancer dissemination. The expression associations between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and KI-67 have also been examined in 114 patients with colorectal cancer who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry tissue microarray methods were performed in samples from the primary tumors. The gene expression results showed that the ITGA-3 and ITGB-5 genes were overexpressed in tumors with lymph node and distant metastasis (III/IV-stage tumors compared with I/II tumors). The MMP-2 gene showed significant overexpression in mucinous type tumors, and MMP-9 was overexpressed in villous adenocarcinoma histologic type tumors. The ECM genes MMP9 and ITGA-3 have shown a significant expression correlation with EGFR epithelial marker. The overexpression of the matrix extracellular genes ITGA-3 and ITGB-5 is associated with advanced stage tumors, and the genes MMP-2 and MMP-9 are overexpressed in mucinous and villous adenocarcinoma type tumors, respectively. The epithelial marker EGFR overactivity has been shown to be associated with the ECM genes MMP-9 and ITGA-3 expression. Suzana Angelica Silva Lustosa, Luciano de Souza Viana, Renato José Affonso Jr., Sandra Regina Morini Silva, Marcos Vinicius Araujo Denadai, Silvia Regina Caminada de Toledo, Indhira Dias Oliveira, and Delcio Matos Copyright © 2014 Suzana Angelica Silva Lustosa et al. All rights reserved. Pharmacological Correction of Stress-Induced Gastric Ulceration by Novel Small-Molecule Agents with Antioxidant Profile Sun, 09 Feb 2014 11:09:34 +0000 This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenyl)thioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance. Konstantin V. Kudryavtsev, Anna O. Markevich, Oleksandr V. Virchenko, Tetyana M. Falalyeyeva, Tetyana V. Beregova, Lyudmyla I. Ostapchenko, Dmitry V. Zabolotnev, and Nikolay S. Zefirov Copyright © 2014 Konstantin V. Kudryavtsev et al. All rights reserved. Amelioration of Severe TNBS Induced Colitis by Novel AP-1 and NF-κB Inhibitors in Rats Thu, 30 Jan 2014 07:56:34 +0000 AP-1 and NF-κB inhibitors, namely, DTCM-G and DHMEQ, were investigated in male Wistar rats with severe colitis, induced by TNBS. The animals were randomized into 3 groups. The control group received 0.5 mL of 0.5% of the vehicle i.p., the DTCM-G group received 22.5 mg/kg body weight DTCM-G in 0.5% i.p., and the DHMEQ group received 15 mg/kg body weight DHMEQ i.p., all twice daily for 5 days. The body weight losses and mortality rates were significantly higher in the control group than those in DTCM-G-treated and DHMEQ-treated groups. The endoscopic inflammation scores in the control, DTCM-G-treated, and DHMEQ-treated groups were 6.3 ± 0.7, 1.0 ± 0.3, and 0.7 ± 0.3, respectively (P = 0.004 and 0.02, resp.). The inflammation scores as assessed by the macroscopic appearance were 4.3 ± 0.8, 0.7 ± 0.3, and 1.2 ± 0.4 in the control, DTCM-G-treated, and DHMEQ-treated groups, respectively (P = 0.01 and 0.009, resp.). The histopathological inflammation scores were 6.4 ± 0.7, 2.0 ± 1.0, and 2.2 ± 0.6 in the control, DTCM-G-treated, and DHMEQ-treated groups, respectively (P = 0.03 and 0.01, resp.). It was concluded that DTCM-G and DHMEQ exhibit strong anti-inflammatory and anticancer activities with no apparent toxicity, which make them excellent drug candidates for clinical use in inflammatory bowel diseases. Magdy El-Salhy, Kazuo Umezawa, Odd Helge Gilja, Jan G. Hatlebakk, Doris Gundersen, and Trygve Hausken Copyright © 2014 Magdy El-Salhy et al. All rights reserved. Association of Helicobacter pylori Infection with Coronary Artery Disease: Is Helicobacter pylori a Risk Factor? Thu, 16 Jan 2014 11:56:06 +0000 Background. Helicobacter pylori (HP) infection is the most common infection in the world and coronary artery disease (CAD) is probably associated with it. The aim of this prospective study was to evaluate the association between HP infection and CAD in suspected patients referred for coronary angiography. The coronary angiography was performed using Judkins method and patients were assigned to participate in CAD positive (>50% luminal diameter stenosis) and negative groups. The serum HP IgG antibody was checked. Results. Positive and negative CAD groups consisted of 62 and 58 patients, respectively. HP was more prevalent among CAD+ patients, and with increasing the number of coronary arteries with stenosis, the HP seropositivity increased so that 76.3% of patients with multiple vessel diseases (MVD) and 70% of patients with single vessel diseases (SVD) were HP seropositive versus 50% in control group (). Positive CAD was significantly associated with HDL level () and ESR level (). Also, CAD+ patients had higher CRP levels than controls and it was statistically different between SVD group and controls (). Conclusion. HP infection is more prevalent in CAD positive patients and, in case of proving causal relationship, it can be considered as a reversible risk factor for CAD. Jamshid Vafaeimanesh, Seyyed Fakhroldin Hejazi, Vahid Damanpak, Mostafa Vahedian, Mohammadamin Sattari, and Mohammadreza Seyyedmajidi Copyright © 2014 Jamshid Vafaeimanesh et al. All rights reserved. Feasibility of Endoscopy-Assisted Laparoscopic Full-Thickness Resection for Superficial Duodenal Neoplasms Thu, 16 Jan 2014 11:43:10 +0000 Background. Superficial duodenal neoplasms (SDNs) are a challenging target in the digestive tract. Surgical resection is invasive, and it is difficult to determine the site and extent of the lesion from outside the intestine and resect it locally. Endoscopic submucosal dissection (ESD) has scarcely been utilized in the treatment of duodenal tumors because of technical difficulties and possible delayed perforation due to the action of digestive juices. Thus, no standard treatments for SDNs have been established. To challenge this issue, we elaborated endoscopy-assisted laparoscopic full-thickness resection (EALFTR) and analyzed its feasibility and safety. Methods. Twenty-four SDNs in 22 consecutive patients treated by EALFTR between January 2011 and July 2012 were analyzed retrospectively. Results. All lesions were removed en bloc. The lateral and vertical margins of the specimens were negative for tumor cells in all cases. The mean sizes of the resected specimens and lesions were 28.9 mm (SD ± 10.5) and 13.3 mm (SD ± 11.6), respectively. The mean operation time and intraoperative estimated blood loss were 133 min (SD ± 45.2) and 16 ml (SD ± 21.1), respectively. Anastomotic leakage occurred in three patients (13.6%) postoperatively, but all were minor leakage and recovered conservatively. Anastomotic stenosis or bleeding did not occur. Conclusions. EALFTR can be a safe and minimally invasive treatment option for SDNs. However, the number of cases in this study was small, and further accumulations of cases and investigation are necessary. Ken Ohata, Masahiko Murakami, Kimiyasu Yamazaki, Kouichi Nonaka, Nobutsugu Misumi, Tomoaki Tashima, Yohei Minato, Meiko Shozushima, Takahiro Mitsui, Nobuyuki Matsuhashi, and Kuangi Fu Copyright © 2014 Ken Ohata et al. All rights reserved. Colorectal Surgery in Cirrhotic Patients Wed, 15 Jan 2014 16:02:10 +0000 Patients with cirrhosis have a greater risk of morbidity and mortality following colorectal surgery. Therefore, preoperative medical optimization and risk assessment using criteria such as the MELD score are vital in preventing complications. Some risk factors include age, urgency of surgery, and ASA score. Postoperative morbidity and mortality are related to portal hypertension, ascites, infection, and anastomotic and stomal complications. This review highlights the assessment of risk and perioperative management of cirrhotic patients undergoing colorectal surgery. Jacqueline Paolino and Randolph M. Steinhagen Copyright © 2014 Jacqueline Paolino and Randolph M. Steinhagen. All rights reserved. Assessment of the Body Composition and the Loss of Fat-Free Mass through Bioelectric Impedance Analysis in Patients Who Underwent Open Gastric Bypass Thu, 09 Jan 2014 12:43:05 +0000 Background. Bariatric surgery is considered an effective option for the management of morbid obesity. The incidence of obesity has been gradually increasing all over the world reaching epidemic proportions in some regions of the world. Obesity can cause a reduction of up to 22% in the life expectancy of morbidly obese patients. Objective. The objective of this paper is to assess the weight loss associated with the first 6 months after bariatric surgery using bioelectric impedance analysis (BIA) for the evaluation of fat mass and fat-free mass. Method. A total of 36 morbidly obese patients were subjected to open gastric bypass surgery. The patients weight was monitored before and after the procedure using the bioelectric impedance analysis. Results. Bariatric surgery resulted in an average percentage of weight loss of 28.6% (40 kg) as determined 6 months after the procedure was performed. Analysis of the different components of body weight indicated an undesirable loss of fat-free mass along with the reduction of total body weight. Conclusion. Open gastric bypass induced a significant loss of total weight and loss of fat-free mass in patients six months after the surgery. The use of bioelectric impedance analysis resulted in an appropriate estimation of the total weight components in individuals subjected to bariatric surgery allowing a more real analysis of the variation of weight after the surgery. Wilson Rodrigues de Freitas Junior, Elias Jirjoss Ilias, Paulo Kassab, Roberto Cordts, Paulo Gustavo Porto, Francisco Cesar Martins Rodrigues, Mohamed Ibrahim Ali Taha, Paulo Carrara, Isabella de Carvalho Aguiar, Luis Vicente Franco de Oliveira, Osvaldo Castro, and Carlos Alberto Malheiros Copyright © 2014 Wilson Rodrigues de Freitas Junior et al. All rights reserved. The New Nitinol Conformable Self-Expandable Metal Stents for Malignant Colonic Obstruction: A Pilot Experience as Bridge to Surgery Treatment Thu, 02 Jan 2014 14:02:08 +0000 Introduction. Self-expandable metal stents (SEMS) are a nonsurgical option for treatment of malignant colorectal obstruction also as a bridge to surgery approach. The new nitinol conformable stent has improved clinical outcomes in these kinds of patients. We report a pilot experience with nitinol conformable SEMS placement as bridge to surgery treatment in patients with colorectal obstruction. Materials and Methods. Between April and August 2012, we collected data on colonic nitinol conformable SEMS placement in a cohort of consecutive symptomatic patients, with malignant colorectal obstruction, who were treated as a bridge to surgery. Technical success, clinical success, and adverse events were recorded. Results. Ten patients (7 male (70%)), with a mean age of 69.2 ± 10.1, were evaluated. The mean length of the stenosis was 3.6 ± 0.6 cm. Five patients (50%) were treated on an emergency basis. The median time from stent placement to surgery was 16 days (interquartile range 7–21). Technical and clinical success was achieved in all patients with a significant early improvement of symptoms. No adverse events due to the SEMS placement were observed. Conclusion. This pilot study confirmed the important role of nitinol conformable SEMS as a bridge to surgery option in the treatment of symptomatic malignant colorectal obstruction. Roberto Di Mitri and Filippo Mocciaro Copyright © 2014 Roberto Di Mitri and Filippo Mocciaro. All rights reserved. Association of Self-DNA Mediated TLR9-Related Gene, DNA Methyltransferase, and Cytokeratin Protein Expression Alterations in HT29-Cells to DNA Fragment Length and Methylation Status Sun, 29 Dec 2013 11:41:55 +0000 To understand the biologic role of self-DNA bound to Toll-like Receptor 9 (TLR9), we assayed its effect on gene and methyltransferase expressions and cell differentiation in HT29 cells. HT29 cells were incubated separately with type-1 (normally methylated/nonfragmented), type-2 (normally methylated/fragmented), type-3 (hypermethylated/nonfragmented), or type-4 (hypermethylated/fragmented) self-DNAs. Expression levels of TLR9-signaling and proinflammatory cytokine-related genes were assayed by qRT-PCR. Methyltransferase activity and cell differentiation were examined by using DNA methyltransferase (DNMT1, -3A, -3B) and cytokeratin (CK) antibodies. Treatment with type-1 DNA resulted in significant increase in TLR9 expression. Type-2 treatment resulted in the overexpression of TLR9-related signaling molecules (MYD88A, TRAF6) and the IL8 gene. In the case of type-3 treatment, significant overexpression of NFkB, IRAK2, and IL8 as well as downregulation of TRAF6 was detected. Using type-4 DNA, TRAF6 and MYD88A gene expression was upregulated, while MYD88B, IRAK2, IL8, and TNFSF10 were all underexpressed. CK expression was significantly higher only after type-1 DNA treatment. DNMT3A expression could also be induced by type-1 DNA treatment. DNA structure may play a significant role in activation of the TLR9-dependent and even independent proinflammatory pathways. There may be a molecular link between TLR9 signaling and DNMT3A. The mode of self-DNA treatment may influence HT29 cell differentiation. István Fűri, Ferenc Sipos, Sándor Spisák, Gergő Kiszner, Barnabás Wichmann, Andrea Schöller, Zsolt Tulassay, Györgyi Műzes, and Béla Molnár Copyright © 2013 István Fűri et al. All rights reserved. An Evil Backstage Manipulator: Psychological Factors Correlated with Health-Related Quality of Life in Chinese Patients with Crohn’s Disease Thu, 26 Dec 2013 14:25:24 +0000 Health-related quality of life (HRQoL) is recommended as one of essential parameters to evaluate treatment effect and clinical outcome in patients with Crohn’s disease (CD). Recent studies reported that psychological factors might play a role in HRQoL in Western and American CD patients. Sufficient evidences in Chinese CD patients are still unavailable. This study is dedicated to investigate the correlation of various psychological factors with HRQoL in Chinese CD patients. We prospectively collected 40 active and 40 quiescent CD patients in China and found that psychological factors, especially neuroticism and anxiety, significantly correlate with and affect HRQoL in both active and quiescent CD groups. This is the first report revealing correlation between psychological factors and HRQoL in Chinese CD patients. Therefore, we assume that our results can contribute to a better understanding of etiology and tailoring of management in Chinese patients with Crohn’s disease and are beneficial to our colleagues to compare the heterogeneous characteristics of Crohn’s disease in different ethnic groups. Song Liu, Jianan Ren, Zhiwu Hong, Xiaoting Li, Min Yao, Dongsheng Yan, Huajian Ren, Xiuwen Wu, Gefei Wang, Guosheng Gu, Qiuyuan Xia, Gang Han, and Jieshou Li Copyright © 2013 Song Liu et al. All rights reserved. Profiling the Prognosis of Gastric Cancer Patients: Is It Worth Correlating the Survival with the Clinical/Pathological and Molecular Features of Gastric Cancers? Tue, 24 Dec 2013 11:50:19 +0000 Background. The prognosis of gastric cancer patients still remains poor. The aim of this study was investigating the prognostic value of several clinical/pathological/molecular features in a consecutive series of gastric cancers. Methods. 150 R0 gastrectomies plus 77 gastric cancer patients evaluated for the HER2 overexpression were selected. Survival was calculated and patients stratified according to the stage, the T-stage, the LNRs, the LNH, and the HER2 scoring system. ROC curves were calculated in order to compare the performance of the LRN and LNH systems. Results. Prognosis correlated with the stage and with the T-stage. We documented a statistical correlation between the LNRs and the survival. Conversely, a LNH > 15 did not correlate with the outcomes. The ROC curves documented a significant performance of the LRN system, whereas a statistical correlation was documented for the LNH exclusively with the endpoint of disease-free survival. We documented a trend of worse prognosis for patients with an HER2 overexpression, even though it was not of statistical value. Conclusion. The LNR and the evaluation of the HER2 overexpression might be useful since they correlate with survival, might identify patients with a higher risk of recurrence, and might select patients for a tailored medical treatment. Laura Lorenzon, Paolo Mercantini, Mario Ferri, Marco La Torre, Alessandra Sparagna, Genoveffa Balducci, Giulia Tarantino, Adriana Romiti, Emanuela Pilozzi, and Vincenzo Ziparo Copyright © 2013 Laura Lorenzon et al. All rights reserved. Management of Gastric Varices Unsuccessfully Treated by Balloon-Occluded Retrograde Transvenous Obliteration: Long-Term Follow-Up and Outcomes Sat, 21 Dec 2013 10:37:45 +0000 Our aim was to evaluate the long-term efficacy and safety of percutaneous transhepatic obliteration (PTO) alone and combined with balloon-occluded retrograde transvenous obliteration (BRTO) for gastroesophageal varices refractory to BRTO alone. Between July 1999 and December 2010, 13 patients with gastroesophageal varices refractory to BRTO were treated with PTO (n = 6) or a combination of PTO and BRTO (n = 7). We retrospectively investigated the rates of survival, recurrence, or worsening of the varices; hepatic function before and after the procedure; and complications. The procedure achieved complete obliteration or significant reduction of the varices in all 13 patients without major complications. During follow-up, the varices had recurred in 2 patients, of which one had hepatocellular carcinoma, and the other died suddenly from variceal rebleeding 7 years after PTO. The remaining 11 patients did not experience worsening of the varices and showed significant improvements in the serum ammonia levels and prothrombin time. The mean follow-up period was 90 months, and the cumulative survival rate at 1, 3, and 5 years was 92.9%, 85.7%, and 85.7%, respectively. Both PTO and combined PTO and BRTO seem as safe and effective procedures for the treatment of gastroesophageal varices refractory to BRTO alone. Fumio Uchiyama, Satoru Murata, Shiro Onozawa, Ken Nakazawa, Fumie Sugihara, Daisuke Yasui, Yoshiyuki Narahara, Eiji Uchida, Yasuo Amano, and Shin-ichiro Kumita Copyright © 2013 Fumio Uchiyama et al. All rights reserved. A Thirty-Year Follow-Up Surveillance Study for Neoplasia of a Dutch Ulcerative Colitis Cohort Thu, 28 Nov 2013 15:41:28 +0000 Background. Patients with ulcerative colitis have an increased risk of developing colorectal cancer (CRC). The aim of this study is to assess the yield of surveillance colonoscopies in a tertiary referral cohort of ulcerative colitis patients and to identify different risk groups for dysplasia. Methods. A cohort of 293 patients (148 males, mean age 33.8 years at diagnosis) was built up at our center and started the surveillance program 8–12 years after start of symptoms. They underwent colonoscopies every one to three years. Endpoints were dysplasia or a (sub)total colectomy. Results. After a follow-up period of 10 years, the cumulative incidence of any dysplasia was 23.5%, and of CRC 4.0%. After 15 years these percentages were 33.3% and 6.8%. Patients with pancolitis () had a significantly higher cumulative risk of dysplasia than patients with distal disease, HR 1.9 (95%CI 1.1–3.3). Patients who started surveillance at an older age are at increased risk for any dysplasia, HR 1.03 (95%CI 1.01–1.05). Conclusions. This prospective surveillance study shows a high yield of dysplasia in ulcerative colitis patients. We recommend developing separate surveillance programs for different risk groups. In our opinion patients with distal colitis can follow the general population surveillance program. J. A. M. Stolwijk, A. M. J. Langers, J. C. Hardwick, R. A. Veenendaal, H. W. Verspaget, R. A. van Hogezand, H. F. Vasen, and A. E. van der Meulen-de Jong Copyright © 2013 J. A. M. Stolwijk et al. All rights reserved. Application of Three-Dimensional Imaging to the Intestinal Crypt Organoids and Biopsied Intestinal Tissues Thu, 14 Nov 2013 12:29:50 +0000 Two-dimensional (2D) histopathology is the standard analytical method for intestinal biopsied tissues; however, the role of 3-dimensional (3D) imaging system in the analysis of the intestinal tissues is unclear. The 3D structure of the crypt organoids from the intestinal stem cell culture and intestinal tissues from the donors and recipients after intestinal transplantation was observed using a 3D imaging system and compared with 2D histopathology and immunohistochemistry. The crypt organoids and intestinal tissues showed well-defined 3D structures. The 3D images of the intestinal tissues with acute rejection revealed absence of villi and few crypts, which were consistent with the histopathological features. In the intestinal transplant for megacystis microcolon intestinal hypoperistalsis syndrome, the donor’s intestinal tissues had well-developed nerve networks and interstitial cells of Cajal (ICCs) in the muscle layer, while the recipient’s intestinal tissues had distorted nerve network and the ICCs were few and sparsely distributed, relative to those of the donor. The 3D images showed a clear spatial relationship between the microstructures of the small bowel and the features of graft rejection. In conclusion, integration of the 3D imaging and 2D histopathology provided a global view of the intestinal tissues from the transplant patients. Yun Chen, Ya-Hui Tsai, Yuan-An Liu, Shih-Hua Lee, Sheng-Hong Tseng, and Shiue-Cheng Tang Copyright © 2013 Yun Chen et al. All rights reserved. Review of Inflammatory Bowel Disease in China Thu, 14 Nov 2013 10:24:48 +0000 Inflammatory bowel disease mainly consisting of ulcerative colitis and Crohn’s disease has been rising gradually during the last two decades in China. In this review article, we provide the latest epidemiological trends in incidence, prevalence, and mortality of IBD patients in China and summarize the risk factors and genetic susceptibility of Chinese IBD patients. We also compare these characteristics to those of IBD patients in Western countries. Lingna Ye, Qian Cao, and Jianfeng Cheng Copyright © 2013 Lingna Ye et al. All rights reserved. PLZF Expression during Colorectal Cancer Development and in Normal Colorectal Mucosa according to Body Size, as Marker of Colorectal Cancer Risk Thu, 14 Nov 2013 10:04:13 +0000 Promyelocytic leukemia zinc finger protein (PLZF) is a protein involved in various signaling, growth regulatory, and differentiation pathways, including development/function of some T cells. Here, we aimed at the detection of PLZF during colorectal carcinogenesis, using immunofluorescence, and at the evaluation of the colocalization of PLZF with CD2 and CD56 positive cells (T, γδ, NK, and NKT cells), using confocal-microscopy, along colorectal carcinogenesis, since its earliest stages, that is, dysplastic aberrant crypt foci (ACF). Furthermore, we analyzed PLZF in the normal colonic mucosa (NM) according to anthropometric parameters of the subject. NM exhibited strong CD56 fluorescent staining. This infiltration was lost in both ACF and colorectal carcinoma (CRC), while PLZF presence increased from NM to ACF and CRC. Strong association was found between CD56+ colonic mucosa cell infiltration and body mass index. Interestingly, an increased stromal PLZF-reactivity was present in NM of obese subjects. This study shows that overexpression of PLZF and exclusion of NK cells in dysplastic microenvironment are very early events in the stepwise sequence leading to CRC and that lower levels of CD56+ cells in NM, together with increased levels of PLZF+ cells, can be a reflection of colon cancer risk due to obesity. Francesco Mariani, Paola Sena, Giulia Magnani, Stefano Mancini, Carla Palumbo, Maurizio Ponz de Leon, and Luca Roncucci Copyright © 2013 Francesco Mariani et al. All rights reserved. Prevalence of Functional Gastrointestinal Disorders according to Rome III Criteria in Italian Morbidly Obese Patients Mon, 04 Nov 2013 15:05:01 +0000 The relationship between GI symptoms and obesity has yet to be completely clarified. Aim. To determine in a morbidly obese southern Italy adult population the prevalence of Functional Gastrointestinal Disorders (FGID) and its association with the presence of a Binge Eating (BE) behavior pattern. Methods. Consecutive obese patients eligible for bariatric surgery and 100 Healthy Controls (HC) were recruited. All participants were questioned and scored for the presence of FGID according to Rome III criteria and for the presence or the frequency-intensity of a number of upper and lower GI symptoms. BE behavior pattern was assessed. Results. One-hundred obese patients met the inclusion criteria. The prevalence of FGID was similar between obese patients and HC. There was a significant association between obese patients with BE behavior and postprandial distress syndrome (). Moreover, a significantly higher frequency-intensity score for epigastric fullness ( versus , ) was found in obese patients with BE behavior compared to obese patients without. Conclusions. Obese patients with a BE behavior pattern showed a significantly higher prevalence of postprandial distress syndrome. A greater knowledge of the GI symptoms associated with obesity along with the pathophysiological mechanisms underlying will be important in the clinical management of these patients. Antonella Santonicola, Luigi Angrisani, Carolina Ciacci, and Paola Iovino Copyright © 2013 Antonella Santonicola et al. All rights reserved. Involvement of MAPKs and PLC Pathways in Modulation of Pacemaking Activity by So-Cheong-Ryong-Tang in Interstitial Cells of Cajal from Murine Small Intestine Wed, 30 Oct 2013 08:30:42 +0000 Purpose. Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We have aimed to investigate the effects of Socheongryong-Tang (SCRT) in ICCs from mouse’s small intestine. Methods. The whole-cell patch-clamp configuration was used to record membrane potentials from cultured ICCs. Intracellular Ca2+ () increase was studied in cultured ICCs using fura-2 AM. Results. ICCs generated pacemaker potentials in mouse’s small intestine. SCRT produced membrane depolarization in current clamp mode. Y25130 (5-HT3 receptor antagonist) and RS39604 (5-HT4 receptor antagonist) blocked SCRT-induced membrane depolarizations, whereas SB269970 (5-HT7 receptor antagonist) did not. When GDP-β-S (1 mM) was in the pipette solution, SCRT did not induce the membrane depolarizations. analysis showed that SCRT increased . In the presence of PD98059 (p42/44 MAPK inhibitor), SCRT did not produce membrane depolarizations. In addition, SB203580 (p38 MAPK inhibitor) and JNK inhibitors blocked the depolarizations by SCRT in pacemaker potentials. Furthermore, the membrane depolarizations by SCRT were not inhibited by U-73122, an active phospholipase C (PLC) inhibitor, but by U-73343, an inactive PLC inhibitor. Conclusion. These results suggest that SCRT might affect GI motility by the modulation of pacemaker activity through MAPKs and PLC pathways in the ICCs. Min Woo Hwang, Hee Jung Lee, Ho Joon Song, and Byung Joo Kim Copyright © 2013 Min Woo Hwang et al. All rights reserved. Effect of Vasoactive Intestinal Peptide (VIP) on NKG2D Signal Pathway and Its Contribution to Immune Escape of MKN45 Cells Sun, 20 Oct 2013 14:45:06 +0000 Objective. To investigate VIP effect on the cytotoxicity of NK cell to gastric cancer cells in vitro and the relation between the effect with the NKG2D signal molecules in NK cells. Material and Methods. NK cells were purified from peripheral blood mononuclear cells (PBMC). Before and after NK cells were incubated with VIP or its antagonist (D-p-Cl-Phe6,Leu17)-VIP, we detected the cytotoxicity of NK cells to MKN45 gastric cancer cells by MTT and detected the expressions of NKG2D, DAP10, and NF-κB proteins and mRNAs in NK cells by immunocytochemistry and RT-PCR in those conditions. Then we analyzed the effect of VIP and its antagonist on the cytotocicity of NK cell to gastric cancer cells and on expressions of NKG2D, DAP10, and NF-κB signal molecules in NK cells. Results. VIP could inhibit the cytotoxicity of NK cells to MKN45 cells and could inhibit the expressions of NKG2D, DAP10, and NF-κB in NK cells. However, (D-p-Cl-Phe6, Leu17)-VIP could reverse those effects. Conclusions. The VIP inhibited the cytotoxicity of NK cell to MKN45 cells which might get through inhibiting the expressions of NKG2D signal molecules in NK cells. This may be one mechanism of gastric cancer cells escaping organism immune clearance. Chong Wang, Xi-Jin Zhou, Yuan-yuan Li, Juan Wan, Le-ying Yang, and Guo-Hua Li Copyright © 2013 Chong Wang et al. All rights reserved. Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of -tTF Tue, 18 Jun 2013 11:40:26 +0000 Purpose. Truncated tissue factor (tTF) fusion protein targeting tumor vasculature can induce tumor vascular thrombosis and necrosis. Here, we generated (RGD)3-tTF in which three arginine-glycine-aspartic (RGD) targeting integrin and tTF induce blood coagulation in tumor vessels. Methods. The bioactivities of (RGD)3-tTF including coagulation activity, activation, and binding with integrin were performed. The fluorescent labeled (RGD)3-tTF was intravenously injected into tumor-bearing mice and traced in vivo. The tumor growth, volume, blood vessel thrombosis, tumor necrosis, and survival time of mice treated with (RGD)3-tTF were evaluated. Results. The clotting time and activation of (RGD)3-tTF were similar to that of TF () but different with that of RGD (). (RGD)3-tTF presented a higher binding with than that of RGD and TF at the concentration of 0.2 mol/L (). (RGD)3-tTF could specifically assemble in tumor and be effective in reducing tumor growth by selectively inducing tumor blood vessels thrombosis and tumor necrosis which were absent in mice treated with RGD or TF. The survival time of mice treated with (RGD)3-tTF was higher than that of mice treated with TF or RGD (). Conclusion. (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer. Zheng-jie Huang, Yilin Zhao, Wei-yuan Luo, Jun You, Shui-wen Li, Wen-cheng Yi, Sheng-yu Wang, Jiang-hua Yan, and Qi Luo Copyright © 2013 Zheng-jie Huang et al. All rights reserved. Prognostic Factors of Peritoneal Metastases from Colorectal Cancer following Cytoreductive Surgery and Perioperative Chemotherapy Thu, 18 Apr 2013 14:25:33 +0000 Background. Prolonged survival of patients affected by peritoneal metastasis (PM) of colorectal origin treated with complete cytoreduction followed by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has been reported. However, two-thirds of the patients after complete cytoreduction and perioperative chemotherapy (POC) develop recurrence. This study is to analyze the prognostic factors of PM from colorectal cancer following the treatment with cytoreductive surgery (CRS) + POC. Patients and Methods. During the last 8 years, 142 patients with PM of colorectal origin have been treated with CRS and perioperative chemotherapy. The surgical resections consisted of a combination of peritonectomy procedures. Results. Complete cytoreduction (CCR-0) was achieved at a higher rate in patients with peritoneal cancer index (PCI) score less than 10 (94.7%, 71/75) than those of PCI score above 11 (40.2%, 37/67). Regarding the PCI of small bowel (SB-PCI), 89 of 94 (91.5%) patients with ≤2 and 22 of 48 (45.8%) patients with SB-PCI ≥ 3 received CCR-0 resection (). Postoperative Grade 3 and Grade 4 complications occurred in 11 (7.7%) and 14 (9.9%). The overall operative mortality rate was 0.7% (1/142). Cox hazard model showed that CCR-0, SB-PCI ≤ 2, differentiated carcinoma, and PCI ≤ 10 were the independent favorite prognostic factors. Conclusions. Complete cytoreduction, PCI, SB-PCI threshold, and histologic type were the independent prognostic factors. Yutaka Yonemura, Emel Canbay, and Haruaki Ishibashi Copyright © 2013 Yutaka Yonemura et al. All rights reserved. Optimization of Drug Delivery Systems for Intraperitoneal Therapy to Extend the Residence Time of the Chemotherapeutic Agent Mon, 25 Mar 2013 10:14:15 +0000 Intraperitoneal (IP) chemotherapy is an effective way of treating peritoneal carcinomatosis of colorectal origin after complete cytoreduction. Although IP therapy has been already performed for many years, no standardized treatment design has been developed in terms of schedule, residence time, drug, or carrier solution. Because of the fast clearance of the conventional intravenous (IV) drug delivery systems used for IP therapy, a lot of research is performed to optimize IP drug delivery and extend the residence time of the cytotoxic agent in the peritoneal cavity. This paper reviews the recent advances made in drug delivery systems for IP chemotherapy, discussing the use of microparticles, nanoparticles, liposomes, micelles, implants, and injectable depots for IP delivery. L. De Smet, W. Ceelen, J. P. Remon, and C. Vervaet Copyright © 2013 L. De Smet et al. All rights reserved. DNA Damage Sensor γ-H2AX Is Increased in Preneoplastic Lesions of Hepatocellular Carcinoma Sun, 03 Mar 2013 08:23:10 +0000 Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule , which was significantly higher than HCC . Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (, from 5.1 to 96.0%, ). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC. Yasunobu Matsuda, Toshifumi Wakai, Masayuki Kubota, Mami Osawa, Masaaki Takamura, Satoshi Yamagiwa, Yutaka Aoyagi, Ayumi Sanpei, and Shun Fujimaki Copyright © 2013 Yasunobu Matsuda et al. All rights reserved. MicroRNAs in Hepatocellular Carcinoma: Regulation, Function, and Clinical Implications Mon, 04 Feb 2013 14:29:42 +0000 Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Poor understanding of the mechanisms underlying the pathogenesis of HCC makes it difficult to be diagnosed and treated at early stage. MicroRNAs (miRNAs), a class of noncoding single-stranded RNAs of ~22 nucleotides in length, posttranscriptionally regulate gene expression by base pairing with the untranslated regions (UTRs) of target messenger RNAs (mRNAs). Aberrant expression of miRNAs is found in many if not all cancers, and many deregulated miRNAs have been proved to play crucial roles in the initiation and progression of cancers by regulating the expression of various oncogenes or tumor suppressor genes. In this Paper, we will summarize the regulations and functions of miRNAs aberrantly expressed in HCC and discuss the potential application of miRNAs as diagnostic and prognostic biomarkers of HCC and their potential roles in the intervention of HCC. Jie Sun, Haiqi Lu, Xian Wang, and Hongchuan Jin Copyright © 2013 Jie Sun et al. All rights reserved. Sorafenib in Advanced Hepatocellular Carcinoma: A Nationwide Retrospective Study of Efficacy and Tolerability Tue, 29 Jan 2013 08:27:02 +0000 Background. Advanced HCC is a clinical challenge with limited treatment options. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Furthermore we explore the role of alpha-fetoprotein (αFP) as a potential biomarker for treatment efficacy and correlation to survival. Methods. Seventy-six patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib between 2007 and 2009 were included. Followup was until 2011. Results. Patients in PS 0-1 had a median overall survival (mOS) of 6.2 months, compared to 1.8 months in patients with poorer PS (). Child-Pugh A patients had a mOS of 6.6 months versus 3.6 months among patients in Child-Pugh B or C (). Serum αFP ≥ 200 at baseline was prognostic for a shorter survival. All patients with radiologically verified tumor response and baseline αFP ≥ 200 experienced a significant decline in αFP within the first four weeks of treatment. Conclusion. The survival of patients with advanced HCC treated with sorafenib is dependent on performance status and liver function. Treatment of patients with compromised liver function and poor performance status cannot be recommended. The correlation between αFP and objective tumor response warrants further investigation. Anne Helene Køstner, Morten Sorensen, René Krøjgaard Olesen, Henning Grønbæk, Ulrik Lassen, and Morten Ladekarl Copyright © 2013 Anne Helene Køstner et al. All rights reserved. Goblet Cell Carcinoids of the Appendix Mon, 14 Jan 2013 09:08:34 +0000 Goblet cell carcinoid (GCC) tumors are a rare subgroup of neuroendocrine tumors almost exclusively originating in the appendix. The tumor most often presents in the fifth or sixth decade with a clinical picture of appendicitis or in advanced cases an abdominal mass associated with abdominal pain. Histologically tumors are most often positive for chromogranin A and synaptophysin, however, less homogenous than for classic appendix carcinoids. The malignant potential is higher than that for the classic appendix carcinoids due to local spread and distant metastases at diagnosis and the proliferation markers (Ki67 index) may determine prognosis. Octreotide receptor scintigraphy is usually negative while CT/MRI scans may be useful. Chromogranin A is usually negative and other biomarkers related to the mucinous component or the tumor (CEA, CA-19-9, and CA-125) may be used. Surgery is the main treatment with appendectomy and right hemicolectomy while patients with disseminated disease should be treated with chemotherapy. Overall 5-year survival is approximately 75%. The diagnosis and treatment of GCC tumorss should be restricted to high volume NET centers in order to accumulate knowledge and improve survival in GCC NET patients. The aim of this paper is to update on epidemiology, clinical presentation, and diagnostic markers including Ki67 index, treatment, and survival. Nanna Holt and Henning Grønbæk Copyright © 2013 Nanna Holt and Henning Grønbæk. All rights reserved. Sorafenib Inhibits Tumor Growth and Improves Survival in a Transgenic Mouse Model of Pancreatic Islet Cell Tumors Thu, 27 Dec 2012 10:49:11 +0000 Background. The purpose of the study was to evaluate Sorafenib (BAY 43-9006) derived receptor tyrosine kinase inhibition on tumor progression in murine islet cell tumors. Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors. Rip1Tag2 mice were treated in two different groups according to the model of tumor progression: the early treatment group received vehicle or Sorafenib from 10 to 14 weeks of age and the late treatment group from week 12 until death. Tumor surface, tumor cell proliferation, and apoptosis were measured in both treatment groups to assess the in vivo effects of Sorafenib. Survival was recorded for the late treatment group. In the early treatment group Sorafenib led to a dramatic decrease in tumor volume compared to the control group. Apoptosis was significantly augmented and cell proliferation was inhibited. As a single therapy Sorafenib significantly improved survival in the late treatment group. Conclusion. Sorafenib may provide a new paradigm for the therapy of islet cell tumors. Volker Fendrich, Katja Maschuw, Johannes Rehm, Malte Buchholz, Julia P. Holler, Emily P. Slater, Detlef K. Bartsch, and Jens Waldmann Copyright © 2012 Volker Fendrich et al. All rights reserved. Clinical Impact of Endoscopic Submucosal Dissection for Gastric Neuroendocrine Tumors: A Retrospective Study from Mainland of China Sun, 23 Dec 2012 10:03:17 +0000 As a minimally invasive technique, endoscopic resection may benefit patients diagnosed with early stage gastrointestinal neuroendocrine tumors (NETs). However, no studies have yet been published in which endoscopic submucosal dissection (ESD) has been applied for gastric NETs. For the first time a research group in China applied ESD to remove gastric NETs, and indicated that ESD should be considered for treatment of eligible gastric NETs because the technique shows a high histologically complete resection rate, provides accurate histopathological evaluation, has a low complication rate, and can be performed within a reasonable timeframe. Wei-Feng Chen, Ping-Hong Zhou, Quan-Lin Li, Mei-Dong Xu, and Li-Qing Yao Copyright © 2012 Wei-Feng Chen et al. All rights reserved. Surgical Treatment of Sporadic Pancreatic Neuroendocrine Tumors: A State of the Art Review Mon, 10 Dec 2012 13:34:30 +0000 Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms. They are clinically diverse and divided into functioning and nonfunctioning disease, depending on their ability to produce symptoms due to hormone production. Surgical resection is the only curative treatment and remains the cornerstone therapy for this patient group, even in patients with advanced disease. Over the last decade there has been a noticeable trend towards more aggressive surgery as well as more minimally invasive surgery in patients with PNETs. This has resulted in improved long-term survival in patients with locally advanced and metastatic disease treated aggressively, as well as shorter hospital stays and comparable long-term outcomes in patients with limited disease treated minimally invasively. There are still controversies related to issues of surgical treatment of PNETs, such as to what extent enucleation, lymph node sampling, and vascular reconstruction are beneficial for the oncologic outcome. Histopathologic tumor classification is of high clinical importance for treatment planning and prognostic evaluation of patients with PNETs. A constant challenge, which relates to the treatment of PNETs, is the lack of an internationally accepted histopathological classification system. This paper reviews current issues on the surgical treatment of sporadic PNETs with specific focus on surgical approaches and tumor classification. Sven-Petter Haugvik, Knut Jørgen Labori, Bjørn Edwin, Øystein Mathisen, and Ivar Prydz Gladhaug Copyright © 2012 Sven-Petter Haugvik et al. All rights reserved. Incidence and Survival of Patients with Small Intestinal Neuroendocrine Tumours in a Danish NET Center Wed, 28 Nov 2012 07:36:42 +0000 Introduction. Small intestinal neuroendocrine tumours (NETs) have increased in incidence during the past decades. In recent years, new promising treatment modalities have been introduced. The aim of the present study was to characterize and compare patients with small intestinal NET seen in the periods 1994–2003 (group 1) and 2004–2011 (group 2) to demonstrate changes in incidence and survival in the two time periods. Patients and Methods. There were 52 NET patients in group 1 and 109 patients in group 2. Results. The incidence of small intestinal NET was 0.3/100.000/year in period 1 and 0.7/100.000/year in period 2. There was no difference in median chromogranin A levels (8709 versus 2381 pmol/L, ), presence of liver metastases (56% versus 44%), clinical symptoms (flushing/diarrhea), or Ki67 index (2% versus 2%), between the two time periods. The 5-year survival rate in the two time periods was similar, 64.7%, and 77.0%, respectively, (). Conclusion. We observed an increase in the incidence of small intestinal NET during the period from January 1994 to December 2011, but we were not able to demonstrate an improved survival during the same time period. Lise Brehm Hoej, Karen Marie Nykjær, and Henning Gronbaek Copyright © 2012 Lise Brehm Hoej et al. All rights reserved. Low Body Mass Index Can Identify Majority of Osteoporotic Inflammatory Bowel Disease Patients Missed by Current Guidelines Thu, 03 May 2012 08:03:28 +0000 Background. Patients with inflammatory bowel disease (IBD) are at high risk of developing osteoporosis. Our objective was to determine the usefulness of IBD guidelines in identifying patients at risk for developing osteoporosis. Methods. We utilized institutional repository to identify patients seen in IBD center and extracted data on demographics, disease history, conventional, and nonconventional risk factors for osteoporosis and Dual Energy X-ray Absorptiometry (DXA) findings. Results. 59% of patients (1004/1703) in our IBD cohort had at least one risk factor for osteoporosis screening. DXA was documented in 263 patients with indication of screening (provider adherence, 26.2%), and of these, 196 patients had DXA completed (“at-risk” group). Ninety-five patients not meeting guidelines-based risk factors also had DXA completed (“not at-risk” group). 139 (70.9%) patients in “at-risk” group had low BMD, while 51 (53.7%) of “not-at-risk” patients had low BMD. Majority of the patients with osteoporosis (83.3%) missed by the current guidelines had low BMI. Multivariate logistic regression analysis showed that low BMI was the strongest risk factor for osteoporosis (OR 3.07; 95% CI, 1.47–6.42; 𝑃=0.003). Conclusions. Provider adherence to current guidelines is suboptimal. Low BMI can identify majority of the patients with osteoporosis that are missed by current guidelines. Ashish Atreja, Ashish Aggarwal, Angelo A. Licata, and Bret A. Lashner Copyright © 2012 Ashish Atreja et al. All rights reserved. Are Ancient Durum Wheats Less Toxic to Celiac Patients? A Study of α-Gliadin from Graziella Ra and Kamut Wed, 02 May 2012 13:33:49 +0000 In the present paper, the controversial hypothesis suggesting ancient grains might show lower immunogenic properties and therefore the possibility to introduce them in the diet of wheat-sensitive people, including celiac patients, was investigated. The immunogenic potential of the ancient durum wheats Graziella Ra and Kamut was studied by comparison to the durum accessions Cappelli, Flaminio, Grazia and Svevo. Experiments were carried out with two monoclonal antibodies (mAbs) raised against α-gliadin peptides p31–49 and p56–75 (the latter containing the overlapping DQ2-Glia-α1 and DQ2-Glia-α2 epitopes), toxic for celiac patients. For all accessions, a few α-gliadin alleles were also cloned, sequenced and translated into aminoacid sequences. Several aminoacid substitutions or deletions were detected in p31–49, DQ2-Glia-α1 and DQ2-Glia-α2 epitopes, nevertheless, ELISA constantly showed antibody-antigen positive reactions which led us to suggest that mAbs binding was not apparently affected by polymorphisms. Moreover, a few substitutions were also observed in DQ2-Glia-α3 and DQ8-Glia-α1 epitopes. Although some DQ2-Glia-α1 and DQ2-Glia-α2 variants evidenced herein were previously reported to have a diminished or abolished T cell stimulatory capacity, present results cannot confirm that ancient durum wheats would be less CD-toxic. In conclusion, we strongly advice celiac patients from consuming ancient wheats including Graziella Ra or Kamut. M. Stella Colomba and Armando Gregorini Copyright © 2012 M. Stella Colomba and Armando Gregorini. All rights reserved. Expressions of MMPs and TIMP-1 in Gastric Ulcers May Differentiate H. pylori-Infected from NSAID-Related Ulcers Tue, 01 May 2012 16:09:48 +0000 Background. Two major causes of gastric ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drug (NSAID) use. Aims. This study aimed to determine if there were different expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) between H. pylori-infected and NSAID-related ulcers. Methods. The 126 gastric ulcer patients (H. pylori infected 𝑛=46; NSAID related 𝑛=30; combined with two factors 𝑛=50) provided ulcer and nonulcer tissues for assessment of MMP-3, -7, and -9 and TIMP-1 expression by immunohistochemical staining. Results. Gastric ulcer tissues had significantly higher MMP-3, -7, and -9 and TIMP-1 expressions than nonulcer tissues (𝑃<0.05). H. pylori-infected gastric ulcers had even higher MMP-7, MMP-9, and TIMP-1 expressions in epithelial cells than NSAID-related gastric ulcers (𝑃<0.05). In patients with the two combined factors, gastric ulcers expressed similar proportions of antral ulcers and MMP-7 and MMP-9 intensities to NSAID-related gastric ulcers, but lower MMP-9 and TIMP-1 than H. pylori-infected gastric ulcers (𝑃<0.05). Conclusions. H. pylori-infected gastric ulcers express higher MMP-7, MMP-9, and TIMP-1 than NSAID-related ulcers. In patients with the two combined factors, ulcer location and MMP-7 and MMP-9 intensities are similar to NSAID use. Hsiu-Chi Cheng, Hsiao-Bai Yang, Wei-Lun Chang, Wei-Ying Chen, Yi-Chun Yeh, and Bor-Shyang Sheu Copyright © 2012 Hsiu-Chi Cheng et al. All rights reserved. Imaging Modalities for the Noninvasive Assessment of Fibrosis in Crohn's Disease Mon, 30 Apr 2012 14:29:34 +0000 The development of strictures in Crohn's disease is a main cause of hospitalization and often represent an indication for surgery. The differentiation between inflammatory and fibrotic strictures is useful to determine the optimal treatment. Today, the availability of noninvasive methods to assess the presence and extension of strictures offers new tools for the diagnosis and follow-up of the disease. Bowel ultrasound, power doppler ultrasound, contrast-enhanced ultrasound, magnetic resonance imaging offer the additional advantage that they do not expose patients to ionizing radiation. In this paper we provide an update on the accuracy of these noninvasive methods for the diagnosis of Crohn's disease. Cristina Stasi, Massimo Falchini, and Stefano Milani Copyright © 2012 Cristina Stasi et al. All rights reserved. Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat Mon, 30 Apr 2012 11:17:24 +0000 Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property. Felipe Meira de-Faria, Ana Cristina Alves Almeida, Anderson Luiz-Ferreira, Christiane Takayama, Ricardo José Dunder, Marcelo Aparecido da Silva, Marcos José Salvador, Patrícia Verardi Abdelnur, Marcos Nogueira Eberlin, Wagner Vilegas, Walber Toma, and Alba Regina Monteiro Souza-Brito Copyright © 2012 Felipe Meira de-Faria et al. All rights reserved. Problem of Foreign Body in GI Tract Thu, 03 Nov 2011 00:00:00 +0000 Most foreign bodies pass through the gastrointestinal tract uneventful. We report of a case of inadvertently ingested foreign body, which by endoscopy simulated a polyp and on biopsy reported as cancer, so the patient underwent an unnecessary major operation. This report emphasizes the importance of resemblance of foreign bodies with gastrointestinal neoplasm, and endoscopists, surgeons and pathologists should consider this entity in their daily practice. Yahya Daneshbod, Abdolrasoul Talei, Shahrzad Negahban, Hossein Soleimanpour, Azita Aledavoud, Neda Bagheri, Mahsa Khanlari, and Khosrow Daneshbod Copyright © 2011 Yahya Daneshbod et al. All rights reserved. Taurine Prevents Ibuprofen-Induced Gastric Mucosal Lesions and Influences Endogenous Antioxidant Status of Stomach in Rats Mon, 01 Jan 1900 00:00:00 +0000 Recently, free radical–induced tissue damage is implicated in the nonsteroidal anti-inflammatory drugs (NSAIDs)–involved gastric mucosal lesion. Administration of taurine, an endogenous antioxidant, is reported to be beneficial in various clinical conditions. Therefore, we decided to study the protective effect of taurine in ibuprofen-induced gastropathy and the effects of administration of taurine on the endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and reduced glutathione (GSH) of stomach. In rats, administration of taurine orally for three consecutive days (250 mg/kg body weight) protected the gastric mucosa from ibuprofen-induced, acute gastric mucosal lesion. In ibuprofen-treated rats, the lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS), a marker for free radical–induced tissue damage, is also significantly decreased by taurine. Ibuprofen treatment resulted in a significant increase in the activities of total SOD, manganese SOD (Mn-SOD), and GPX and reduced GSH. Taurine administration in ibuprofen-treated rats also showed a significant increase in the activities of the antioxidant enzymes namely total SOD, Mn-SOD, GPX, CAT, and the level of reduced GSH. The activity of copper-zinc SOD enzyme (Cu-Zn SOD) is not affected by ibuprofen or taurine. There is no temporal relation between the antioxidant status of the stomach and the tissue damage following oral administration of ibuprofen or taurine. T. Balasubramanian, M. Somasundaram, and A. John William Felix Copyright © 2004 T. Balasubramanian et al. All rights reserved. Can the Intestine Perform Some Functions of the Kidney? Mon, 01 Jan 1900 00:00:00 +0000 The majority of patients in countries like India and Pakistan with end-stage renal disease (ESRD) die without renal replacement therapy due to lack of adequate resources. The use of the intestinal mucosa as a semipermeable membrane for removal of urea and creatinine from the body has been previously studied using various types of intestinal lavage for gut dialysis. This study was undertaken in an animal model to assess the applicability, cost of therapy, and acceptability of the method for potential application in humans. Renal failure was induced in six dogs by bilateral ureteric ligation along with six healthy controls. Dialysis fluid was introduced per rectum as an enema, which was repeatedly administered. Clearances of serum creatinine and urea were assessed. Mean recovery of creatinine and urea in dialysate in the present study was around 8.925 mmol/l and around 207.74 μmol//l, respectively. The mean clearances of serum creatinine and urea were, respectively, 0.0683 and 0.0633 ml/sec. Enteral dialysis was effective and, considering its minimal cost (monthly cost will be around US$35–40) vis a vis available methods, it holds promise for the treatment of patients with ESRD. The creation of an appendicostomy for repeated introduction of antegrade enemas would be a consideration. Uday Sankar Chatterjee, Gopal Samanta, Pallab Pradhan, Provat K. Samanta, and Tapan K. Mondal Copyright © 2007 Uday Sankar Chatterjee et al. All rights reserved. Pancreatic Cancer: Molecular, Biochemical, Chemopreventive, and Therapeutic Aspects Mon, 01 Jan 1900 00:00:00 +0000 Pancreatic cancer (PC) is the fourth leading cause of cancer death, with a median survival of 6 months and a dismal 5-year survival rate of 3–5%, a figure which has remained relatively unchanged over the past 25 years. PC is one of the most difficult diseases to treat due to late initial diagnosis and to resistance to the usual treatments. The presence of occult or clinical metastases at the time of diagnosis, together with the lack of effective chemotherapies, contributes to the high mortality in patients with PC. Its lethal nature stems from its propensity to disseminate rapidly to the lymphatic system and distant organs. Yet, understanding and stopping metastasis may prove to be one of the great potential strategies of treating PC. There is a dire need for the design of new and targeted therapeutic strategies that can overcome the drug resistance and improve the clinical outcome for patients diagnosed with the illness. The knowledge of the molecular aspects of PC is very important, and it is likely to be helpful in the design of newer drugs and the molecular selection of existing agents for targeted therapy. The inhibition of signal pathways can be carried out not only by small molecules, able to bind to selected regions of the target protein, but also by using large molecules as antibodies. The pathway to successful new therapies has been inhibited because of the rapidity with which agents tend to move into randomized, controlled trials without the extensive early testing necessary to optimize treatment regimens. However, lessons have been learned and our collective research effort has generated a substantial platform of knowledge from which further work will spring. The bioavailability of compounds such as antisense oligonucleotides and siRNAs in humans remains a big hurdle, which will require further improvement of gene-delivery strategies. Finally, the long-term goal of the therapy individualization for patients is possible if factors that predict treatment response, such as biological markers, could be determined accurately. These approaches are likely to comprise a mixture of targeted agents in combination with conventional chemotherapy and radiotherapy. For a clinically significant effect to be achieved, treatment strategies should either be in the form of (1) a “horizontal” approach, in which several oncogenic pathways (as those described in this series of reviews) are inhibited; or (2) a “vertical” approach, whereby multiple levels of a major pathway are targeted. Combination therapies, together with improved diagnostic tools and predictive markers, are ultimately desired in order to improve the bleak outlook for patients diagnosed with PC. Juan Iovanna and José Luis Neira Copyright © 2010 Juan Iovanna and José Luis Neira. All rights reserved. Adult Intussusception Presenting with Target Sign Mon, 01 Jan 1900 00:00:00 +0000 Emmanuel C. Gorospe Copyright © 2008 Emmanuel C. Gorospe. All rights reserved. Ruptured Jejunal Diverticulum Due to a Single-Band Small Bowel Obstruction Mon, 01 Jan 1900 00:00:00 +0000 Jejunal diverticulosis is rare and often goes unnoticed until complications occur. The diverticula are true, acquired diverticula and often asymptomatic. Jejunal diverticulosis can be associated with diverticulosis of the duodenum, ileum, and colon. Here we describe a patient with known severe diverticular disease of the large bowel, who presented acutely with abdominal pain and signs of generalised peritonitis. Laparotomy showed ruptured jejunal diverticulosis with a single band over the terminal ileum, causing small bowel obstruction. Spontaneous perforation of a jejunal diverticulum is rare and is usually an intraoperative finding. One should exclude a precipitating cause, such as coexisting distal obstruction, stricture, or a foreign body. Rajaraman Durai, Ashish Sinha, Mihir Khan, Happy Hoque, and Rajab Kerwat Copyright © 2008 Rajaraman Durai et al. All rights reserved. Heparin and Insulin for Hypertriglyceridemia-Induced Pancreatitis: Case Report Mon, 01 Jan 1900 00:00:00 +0000 Hypertriglyceridemia is the etiology of acute nonbiliary pancreatitis in up to 3% of patients. Along with the supportive treatment of acute pancreatitis, treating the precipitating cause is important as well. There have been reports where heparin and insulin have been used for acute reduction of triglycerides, although there are no established guidelines for efficacy of these modalities. Heparin and insulin decrease triglycerides by stimulating lipoprotein lipase activity, which degrades triglycerides into fatty acids and glycerol. We present a case where a 54-year-old male presented with hypertriglyceridemia-induced acute pancreatitis. The serum triglyceride level was 10,320 mg/dl (normal: 0–15 mg/dl) at the time of admission. We started the patient on intravenous insulin and heparin infusion, and within 24 h of induction of treatment, the levels decreased by 50% to 5407 mg/dl. Thus, heparin and insulin can be considered a safe treatment modality for rapidly reducing triglyceride levels. Deepika Jain and John Zimmerschied Copyright © 2009 Deepika Jain and John Zimmerschied. All rights reserved. Radical Pancreaticoduodenectomy for Benign Disease Mon, 01 Jan 1900 00:00:00 +0000 Whipple's procedure is the treatment of choice for pancreatic and periampullary malignancies. Preoperative histological confirmation of malignancy is frequently unavailable and some patients will subsequently be found to have benign disease. Here, we review our experience with Whipple's procedure for patients ultimately proven to have benign disease. The medical records of all patients who underwent Whipple's procedure during a 15-year period (1987–2002) were reviewed; 112 patients underwent the procedure for suspected malignancy. In eight cases, the final histology was benign (7.1%). One additional patient was known to have benign disease at resection. The mean age was 50 years (range: 30–75). The major presenting features included jaundice (five), pain (two), gastric outlet obstruction (one), and recurrent gastrointestinal haemorrhage (one). Investigations included ultrasound (eight), computerised tomography (eight), endoscopic retrograde cholangiopancreatography (seven; of these, four patients had a stent inserted and three patients had sampling for cytology), and endoscopic ultrasound (two). The pathological diagnosis included benign biliary stricture (two), chronic pancreatitis (two), choledochal cyst (one), inflammatory pseudotumour (one), cystic duodenal wall dysplasia (one), duodenal angiodysplasia (one), and granular cell neoplasm (one). There was no operative mortality. Morbidity included intra-abdominal collection (one), anastomotic leak (one), liver abscess (one), and myocardial infarction (one). All patients remain alive and well at mean follow-up of 41 months. Despite recent advances in diagnostic imaging, 8% of the patients undergoing Whipple'’s procedure had benign disease. A range of unusual pathological entities can mimic malignancy. Accurate preoperative histological diagnosis may have allowed a less radical operation to be performed. Endoscopic ultrasound–guided fine needle aspirate (EUS-FNA) may reduce the need for Whipple's operation in benign pancreaticobiliary disease in the future. D. O. Kavanagh, C. O'Riain, P. F. Ridgway, P. Neary, T. C. Crotty, J. G. Geoghegan, and O. Traynor Copyright © 2008 D. O. Kavanagh et al. All rights reserved. Unusual Case Report of Thrombotic Microangiopathy of the Small Bowel Following Liver Transplantation, a Possible Immunosuppressant-Induced Disease with Histological and Ultrastructural Findings Mon, 01 Jan 1900 00:00:00 +0000 Cyclosporin-A (CsA) and tacrolimus (FK-506) are immunomodulating agents used to prevent rejection in organ transplantation. They are both associated with several side effects, including nephrotoxicity and severe hypertension due to vascular injury, which often appears as a microvascular occlusive disorder (thrombotic microangiopathy, TMA). We report the first case of a microvascular occlusive disorder with the features of TMA in the small bowel of an orthotopic liver transplant (OLT) patient after immunosuppressive therapy with CsA and FK506. The patient presented with severe recurrent abdominal colics and distal subocclusion, requiring aggressive surgical treatment. Histological and ultrastructural analysis of the resected specimen disclosed intestinal TMA. Although rare, such a complication should be considered in the differential diagnosis of abdominal colics in patients undergoing immunosuppressant therapy after OLT. Domenico Piscitelli, Maria Grazia Fiore, Roberta Rossi, Michelina Casiello, and Francesca Sanguedolce Copyright © 2009 Domenico Piscitelli et al. All rights reserved. Epithelial-to-Mesenchymal Transition in Pancreatic Adenocarcinoma Mon, 01 Jan 1900 00:00:00 +0000 Epithelial to mesenchymal transition (EMT) is a physiologic process that allows morphological and genetic changes of carcinoma cells from an epithelial to a mesenchymal phenotype, which is the basis of the high metastatic potential of pancreatic cancer cells. EMT is triggered by various tumor microenvironmental factors, including cytokines, growth factors, and chemotherapeutic agents. This review summarizes the state-of-the-art knowledge on the molecular mechanisms that support pancreatic cancer EMT and the evidences that support its involvement in invasiveness/aggressiveness, and the drug resistance of pancreatic cancer cells. Carla Cano, Yoshiharu Motoo, and Juan L. Iovanna Copyright © 2010 Carla E. Cano et al. All rights reserved. The Safety and Efficacy of a Mixture of Honey, Olive Oil, and Beeswax for the Management of Hemorrhoids and Anal Fissure: A Pilot Study Mon, 01 Jan 1900 00:00:00 +0000 We have found that a mixture of honey, olive oil, and beeswax was effective for treatment of diaper dermatitis, psoriasis, eczema, and skin fungal infection. The mixture has antibacterial properties. A prospective pilot study was conducted to evaluate the therapeutic effect of topical application of the mixture on patients with anal fissure or hemorrhoids.Fifteen consecutive patients, 13 males and 2 females, median age 45 years (range: 28–70), who presented with anal fissure (5 patients) or first- to third-degree hemorrhoids (4 with first degree, 4 with second degree, and 2 with third degree), were treated with a 12-h application of a natural mixture containing honey, olive oil, and beeswax in ratio of 1:1:1(v/v/v). Bleeding, itching, edema, and erythema were measured using a scoring method: 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe. The pain score was checked using a visual analog scale (minimum = 0, maximum = 10). Efficacy of treatment was assessed by comparing the symptoms' score before and after treatment; at weekly intervals for a maximum of 4 weeks. The patients were observed for evidence of any adverse effect such as appearance of new signs and symptoms, or worsening of the existing symptoms. The honey mixture significantly reduced bleeding and relieved itching in patients with hemorrhoids. Patients with anal fissure showed significant reduction in pain, bleeding, and itching after the treatment. No side effect was reported with use of the mixture. We conclude that a mixture of honey, olive oil, and beeswax is safe and clinically effective in the treatment of hemorrhoids and anal fissure, which paves the way for further randomized double blind studies. Noori S. Al-Waili, Khelod S. Saloom, Thia N. Al-Waili, and Ali N. Al-Waili Copyright © 2006 Noori S. Al-Waili et al. All rights reserved. CD73-Dependent Regulation of Interferon AlphaA and Interleukin-10 in the Inflamed Mucosa Mon, 01 Jan 1900 00:00:00 +0000 The ecto-5'-nucleotidase, CD73, catalyzes the rate-limiting step in the phosphohydrolysis of ATP to adenosine, and is a critical regulator of the balance between adenosine and its nucleotide precursors. Each of these classes of mediators signal through their independent receptor families to regulate downstream inflammatory signaling. CD73 activity is primarily regulated at the level of transcription in response to the oxygen-sensing transcription factor HIF1, and its tissue-specific expression correlates negatively with oxygen tension. HIF1-dependent induction of CD73 contributes to the protective effects of hypoxia in the inflamed intestinal mucosa. These beneficial effects of CD73 have largely been attributed to downstream adenosine signaling through its tissue-specific receptors. In addition, adenosine signaling has been directly implicated in the protective effects of hypoxic preconditioning against acute hypoxic or ischemic insults. However, recent work has demonstrated that CD73-/- animals lack the ability to produce interferon (IFN) αA, either at baseline or in response to inflammation. Furthermore, this IFN-αA deficiency is associated with the inability to elaborate interleukin (IL)-10–dependent anti-inflammatory signaling. It remains unclear whether interruption of IFN-αA and IL-10 signaling in the absence of CD73 activity results from a deficiency of its product adenosine or an accumulation of its substrate nucleotides. Current evidence for adenosine- and nucleotide-mediated mechanisms of tissue inflammation is reviewed below (Fig. 1). Ilya Sotnikov and Nancy A. Louis Copyright © 2010 Ilya Sotnikov and Nancy A. Louis. All rights reserved. Histological Value of Duodenal Biopsies Mon, 01 Jan 1900 00:00:00 +0000 This study was performed to see the value of histopathological diagnosis in management of patients with duodenal biopsies; to look for correlation of histology and serology in suspected cases of coeliac disease; the reasons for taking duodenal biopsies and whether proper adequate histories are provided on the forms sent with request for histopathological view on duodenal biopsies. Here are the observations of the study followed by the discussion. Limci Gupta and Hamid B. Copyright © 2005 Limci Gupta. All rights reserved. Neonatal Necrotizing Enterocolitis Mon, 01 Jan 1900 00:00:00 +0000 Necrotizing enterocolitis (NEC) is a gastrointestinal disease that mostly affects premature infants. It involves infection and inflammation that causes destruction of the bowel. Although it affects only 1 in 2,000 to 4,000 births, or between 1 and 5% of neonatal intensive care unit admissions, NEC is the most common and serious gastrointestinal disorder among hospitalized preterm infants. We present a very representative abdominal X-ray of this disease. Saad Lahmiti and Abdelmounaim Aboussad Copyright © 2011 Saad Lahmiti and Abdelmounaim Aboussad. All rights reserved. Colonic Carcinoma Masquerading as Scrotal Swelling: A Case Report and Review of Literature Mon, 01 Jan 1900 00:00:00 +0000 Tumours of the spermatic cord are rare. Most tumours of the spermatic cord are metastatic and are typically an incidental finding at orchidectomy for other pathology. Primary pathology is usually from the gastrointestinal tract. We report a very rare presentation of an asymptomatic gastrointestinal tumour as a spermatic cord mass. Sharath C. V. Paravastu, Meenakshi Batra, and Krishnan Ananthakrishnan Copyright © 2007 Sharath C. V. Paravastu et al. All rights reserved. Early Satiety — An Unusual Cause Mon, 01 Jan 1900 00:00:00 +0000 Robin AP Weir and Nigel McMillan Copyright © 2006 Robin AP Weir and Nigel McMillan. All rights reserved. Effects of Biphenyldimethyl-dicarboxylate Administration Alone or Combined with Silymarin in the CCL4 Model of Liver Fibrosis in Rats Mon, 01 Jan 1900 00:00:00 +0000 The effect of biphenyldimethyldicarboxylate (DDB), a synthetic compound, in use for the treatment of chronic hepatitis was studied on hepatic injury caused in rats by administration of carbon tetrachloride (CCl4). Starting at time of administration of the first dose of CCl4, rats received DDB at four dose levels (3, 15, 75 or 375 mg/kg), silymarin (22 mg/kg), a combination of DDB (75 mg/kg) and silymarin (22 mg/kg) or saline (control) once orally daily for 30 days. The administration of DDB in CCl4-treated rats at 75 or 375 mg/kg resulted in 61.2-76.2% decrease in alanine aminotransferase (ALT) and 46.9-60.8% decrease in aspartate aminotransferase (AST), respectively compared with the CCl4 control group. Silymarin treatment resulted in 34.6 and 30% decrease in ALT and AST, while DDB (75 mg/kg) combined with silymarin (22 mg/kg) resulted in 58.2 and 31% decrease in ALT and AST, respectively. Serum creatinine increased by 50% by DDB at 375 mg/kg. After treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin, the development of liver necrosis and fibrosis caused by CCl4 was markedly reduced, while after DDB combined with silymarin no DNA aneuploid cells could be observed. The decrease in glycogen and protein contents in hepatocytes caused by CCl4 was markedly prevented by co-treatment with DDB at 75 or 375 mg/kg or DDB combined with silymarin. It is concluded that in the model of hepatic injury caused by chronic administration of CCl4 in rats, the synthetic compound DDB, limits hepatocellular injury and exerts antifibrotic effect. Better improvement in protein, DNA, mucopolysaccharide content was seen after both DDB and silymarin compared to DDB alone. It is suggested, therefore, that DDB alone or in combination with silymarin might prove of benefit in the therapy of chronic liver disease. Monitoring of kidney functions in patients taking DDB is warranted. Omar M. E. Abdel-Salam, Amany A. Sleem, and Fatma A. Morsy Copyright © 2007 Omar M. E. Abdel-Salam et al. All rights reserved. A Novel P53-Related Activity in a Colon Adenocarcinoma Cell Line With Mutant P53 Mon, 01 Jan 1900 00:00:00 +0000 Andrei L. Gartel, Eugene Goufman, Charlotte Hurth, and Angela L. Tyner Copyright © 2001 Andrei L. Gartel et al. All rights reserved. Management of a Ruptured Pseudoaneurysm of Common Hepatic Artery Following Pancreaticoduodenectomy Mon, 01 Jan 1900 00:00:00 +0000 Postoperative pseudoaneurysm formation is one of the most feared complications of pancreatic leak following pancreaticoduodenectomy (PD). Surgical repair may be compromised due to a persistent enzymatic insult on the repaired vessel; therefore, preventive measures should be adopted. We report a case of ruptured hepatic artery pseudoaneurysm occurring 12 days following PD in a patient with a postoperative pancreatic fistula. Emergency surgery revealed that the pseudoaneurysm was situated at the point of surgical transfixation of the gastroduodenal artery. The pseudoaneurysm was successfully managed by under-running of the bleeding point combined with the direct application of hemostatic products to the bleeding surface (TachoSilTM and TisseelTM to act as a barrier from the pancreatic secretions. M. Abu-Hilal, M. J. Hallam, B. A. Zeidan, and N. W. Pearce Copyright © 2007 Mohammed Abu-Hilal et al. All rights reserved. Optical Coherence Tomography Mon, 01 Jan 1900 00:00:00 +0000 Optical coherence tomography (OCT) is an optical imaging modality that performs high-resolution, cross-sectional, subsurface tomographic imaging of the microstructure of tissues. The physical principle of OCT is similar to that of B-mode ultrasound imaging, except that it uses infrared light waves rather than acoustic waves. The in vivo resolution is 10–25 times better (about 10 µm) than with high-frequency ultrasound imaging, but the depth of penetration is limited to 1–3 mm, depending on tissue structure, depth of focus of the probe used, and pressure applied to the tissue surface. In the last decade, OCT technology has evolved from an experimental laboratory tool to a new diagnostic imaging modality with a wide spectrum of clinical applications in medical practice, including the gastrointestinal tract and pancreatico-biliary ductal system. OCT imaging from the gastrointestinal tract can be done in humans by using narrow-diameter, catheter-based probes that can be inserted through the accessory channel of either a conventional front-view endoscope, for investigating the epithelial structure of the gastrointestinal tract, or a side-view endoscope, inside a standard transparent ERCP (endoscopic retrograde cholangiopancreatography) catheter, for investigating the pancreatico-biliary ductal system. The esophagus and esophagogastric junction have been the most widely investigated organs so far; more recently, duodenum, colon, and the pancreatico-biliary ductal system have also been extensively investigated. OCT imaging of the gastrointestinal wall structure is characterized by a multiple-layer architecture that permits an accurate evaluation of the mucosa, lamina propria, muscularis mucosae, and part of the submucosa. The technique may therefore be used to identify preneoplastic conditions of the gastrointestinal tract, such as Barrett's epithelium and dysplasia, and evaluate the depth of penetration of early-stage neoplastic lesions. OCT imaging of the pancreatic and biliary ductal system could improve the diagnostic accuracy for ductal epithelial changes, and the differential diagnosis between neoplastic and non-neoplastic lesions. Pier Alberto Testoni Copyright © 2007 Pier Alberto Testoni. All rights reserved. Acute Hemorrhage into Adrenal Pseudocyst Presenting with Shock: Diagnostic Dilemmas — Report of Three Cases and Review of Literature Mon, 01 Jan 1900 00:00:00 +0000 We report three cases of acutely bleeding adrenal pseudocysts presenting as hemorrhagic shock. Pregnancy was associated in two cases. The diagnostic dilemmas are discussed with special reference to their unusual presentations, diagnosis, and treatment. We believe that our cases, complicated by intracystic hemorrhage, may be related to pregnancy. Amarapathy Sivasankar, Sathyanesan Jeswanth, Maria Antony Johnson, Palaniappan Ravichandran, Shanmugasundaram Rajendran, Devy Gounder Kannan, and Rajagopal Surendran Copyright © 2006 Amarapathy Sivasankar et al. All rights reserved. Syndecan-1 as a Mediator of Bacteria-Enterocyte Interactions Mon, 01 Jan 1900 00:00:00 +0000 Michelle Henry-Stanley and Carol L. Wells Copyright © 2006 Michelle Henry-Stanley and Carol L. Wells. All rights reserved. Gastric Signet-Ring Cell Carcinoma: Unilateral Lower Extremity Lymphoedema as the Presenting Feature Mon, 01 Jan 1900 00:00:00 +0000 Gudrun Lanznaster, Michele Adami, Claudio Crivellaro, Reinhard Kluge, Eduard Egarter-Vigl, and Christian J. Wiedermann Copyright © 2007 Gudrun Lanznaster et al. All rights reserved. Intestinal Ileus as a Possible Cause of Hypobicarbonatemia Mon, 01 Jan 1900 00:00:00 +0000 The possible occurrence of metabolic acidosis in patients with intestinal ileus is not well recognized. We describe a patient with acute alcohol-induced pancreatitis and a large transverse colon ileus in which plasma bicarbonate dropped rapidly in the absence of an increase in the plasma anion gap. The urinary anion gap and ammonium excretion were consistent with an appropriate renal response to metabolic acidosis and against the possibility of respiratory alkalosis. The cause of the falling plasma bicarbonate was ascribed to intestinal bicarbonate sequestration owing to the enhancement of chloride-bicarbonate exchange in a dilated paralyzed colon. Andres Serrano, Rajani K. Chilakapati, Alexander J. Ghanayem, Yemin Yuan, Jeffery Alberts, Cathy Stephen, Giuseppe Rombola, and Daniel Batlle Copyright © 2007 Andres Serrano et al. All rights reserved. TNF-α as a Therapeutic Target in Acute Pancreatitis — Lessons from Experimental Models Mon, 01 Jan 1900 00:00:00 +0000 A considerable body of experimental evidence suggests that tumor necrosis factor (TNF)-α plays a major role in several aspects of inflammation and shock. In particular, it is pivotal in many detrimental effects of acute pancreatitis, and it represents a major determinant of the systemic progression and end-organ damage (such as acute lung injury and liver failure) of this pathologic condition. Given the importance of TNF-α in the pathogenesis of acute pancreatitis, investigators have regarded blocking the action of this mediator as an attractive treatment option. Different specific and nonspecific inhibitors have been developed with promising results in animal models, but, on the other hand, no clinical trials have been designed so far. Difficulties in clinical applications may be multifactorial; experimental models are not fully reliable and reproduce at least some aspects of human disease, timing of intervention should be related to changes in TNF-α serum levels, and inclusion criteria should be accurately selected to better define the population most likely to benefit. Giuseppe Malleo, Emanuela Mazzon, Ajith K. Siriwardena, and Salvatore Cuzzocrea Copyright © 2007 Giuseppe Malleo et al. All rights reserved. Acute Effect of Gamma Irradiation on Gastric Acid Secretion and Gastric Mucosal Integrity in the Rat Mon, 01 Jan 1900 00:00:00 +0000 The effect of 3- or 6-Gray (Gy) whole-body gamma irradiation on basal and stimulated gastric acid secretion was studied in pylorus-ligated rats. Different groups of rats were irradiated with a single 3- or 6-Gy fraction and examined 7 days after irradiation. Exposure to 3-Gy fraction led to marked increase in basal (nonstimulated) gastric acid output in the 4-h pylorus-ligated rat (47.5% compared with unirradiated controls). After exposure to 6 Gy, only 18.2% increase in gastric acid output was noted compared with unirradiated controls. Under pentagastrin or histamine stimulation, gastric acid secretion in those irradiated with 3- or 6-Gy fraction was markedly reduced compared to that of unirradiated controls. Exposure to 3- or 6-Gy gamma irradiation intensified the degree of gastric mucosal injury evoked by indomethacin or 50% ethanol in a dose-dependent manner. It is concluded that in the pylorus-ligated rat model, lower doses of gamma irradiation increase basal gastric acid secretion and impair the gastric mucosal barrier with marked increase in its permeability to H+ following stimulation of acid secretion or exposure to barrier breakers. Exposure to irradiation is likely to result in failure of the parietal cell to respond to direct stimulation with histamine or pentagastrin. Omar M. E. Abdel Salam, Ihsan Hadajat, Ayman Ragab Bayomy, Siham El-Shinawy, and Mahmoud S. Arbid Copyright © 2005 Omar M.E. Abdel Salam et al. All rights reserved. Diaphragm Disease: The Limitation of Laparoscopy and Assessment of the Small Bowel for Strictures Using a Ball Bearing Mon, 01 Jan 1900 00:00:00 +0000 Diaphragm disease is a rare cause of intestinal obstruction that will be seen with increasing frequency with the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs). We present a case study of a patient with diaphragm disease where the diagnosis was not apparent at laparoscopy, and passage of a steel ball through the small intestine was required to identify all strictures present. A high index of suspicion, recognition of the limitations of conventional diagnostic aids, and the need to assess the full length of the small bowel are all important in the surgical management of this condition. C.E. Moffat, M.N. Khyan, C.G. Davies, A.S.K. Ghauri, and C.J. Ranaboldo Copyright © 2006 C.E. Moffat et al. All rights reserved. Epithelial Cell-Neutrophil Interactions in the Alimentary Tract: A Complex Dialog in Mucosal Surveillance and Inflammation Mon, 01 Jan 1900 00:00:00 +0000 Inflammatory diseases of mucosal organs as diverse as the lung, kidney, and intestine, inevitably require the intimate interactions of neutrophils with columnar epithelia. The physiologic consequences of such interactions often determine endpoint organ function, and for this reason, much recent interest has developed in identifying mechanisms and novel targets for the treatment of mucosal inflammation. Elegant in vitro model systems incorporating purified human neutrophils and human epithelial cells grown in physiologic orientations have aided in discovery of new and insightful pathways to define basic inflammatory pathways. Here, we will review the recent literature regarding the interactions between columnar epithelial cells and neutrophils, with an emphasis on intestinal epithelial cells, structural aspects of neutrophil transepithelial migration, molecular determinants of neutrophil-epithelial cell interactions, as well as modulation of these pathways. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation. Sean P. Colgan, Katrina M. Comerford, and Donald W. Lawrence Copyright © 2002 Sean P. Colgan et al. All rights reserved. Congenital Gastric Outlet Obstruction and Nonimmune Hydrops Fetalis: A Prenatal Sonographic Diagnosis of a Case with Hydrothorax and Ascites Mon, 01 Jan 1900 00:00:00 +0000 A case of a male fetus with sonographic diagnosis of hydrops fetalis at 19-week gestation is reported. The fetus had anasarca, bilateral massive pleural effusion, and ascites, in addition to cardiac arrhythmia and congenital gastric outlet obstruction. Mother's clinical history and laboratory workup excluded immune hydrops. The etiological dilemma and fetal outcome are discussed. We concluded, based on this case, that when fetal hydrops occurs early and is associated with multiple congenital anomalies, prolonging the pregnancy may be futile. A. Yisau Abdulkadir, O. A. M. Adesiyun, A. Adisa Fawole, and A. Peter Aboyeji Copyright © 2008 A. Yisau Abdulkadir et al. All rights reserved. Ascites, a New Cause for Bilateral Hydronephrosis: Case Report Mon, 01 Jan 1900 00:00:00 +0000 Bilateral hydronephrosis secondary to urinary obstruction leads to a buildup of back pressure in the urinary tract and may lead to impairment of renal function. We present a case of a 57-year-old male with a history of alcoholic liver cirrhosis, who presented with tense ascites and acute renal failure. Bilateral hydronephrosis was seen on abdominal ultrasound. Multiple large-volume paracenteses resulted in resolution of hydronephrosis and prompt improvement in renal function. Deepika Jain, Smrita Dorairajan, and Madhukar Misra Copyright © 2009 Deepika Jain et al. All rights reserved. Mechanisms of Action of Probiotics in Intestinal Diseases Mon, 01 Jan 1900 00:00:00 +0000 Intestinal microbiota is a positive health asset that exerts a conditioning effect on intestinal homeostasis. Resident bacteria deliver regulatory signals to the epithelium and instruct mucosal immune responses. Recent research has revealed a potential therapeutic role for the manipulation of the microbiota and exploitation of host-microbial signalling pathways in the maintenance of human health and treatment of various mucosal disorders. A variety of pharmabiotic strategies, such as the use of specific members of the microbiota, their surface components, or metabolites, as well as genetically modified commensal bacteria, are being investigated for their ability to enhance the beneficial components of the microbiota. It is clear that engagement with host cells is central to pharmabiotic action, and several strain-specific mechanisms of action have been elucidated. However, the molecular details underpinning these mechanisms remain almost entirely unknown. Understanding how pharmabiotics exert their beneficial effects is critical for the establishment of definitive selection criteria for certain pharmabiotic strategies for specific clinical conditions. Scientifically accredited evidence of efficacy and studies to elucidate the molecular mechanisms of host-microbiota interactions are needed to lend credence to the use of pharmabiotic strategies in clinical medicine. Ann M. O'Hara and Fergus Shanahan Copyright © 2007 Ann O'Hara and Fergus Shanahan. All rights reserved. Lactococcus lactis, A Tool for the Delivery of Therapeutic Proteins Treatment of IBD Mon, 01 Jan 1900 00:00:00 +0000 Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory diseases that consists of ulcerative colitis (UC), an inflammation of the large intestine, and Crohn�s disease (CD), which can affect any part of the gastrointestinal tract. IBD affects approximately 1 in every 1000 individuals in western countries. There is a marked tendency in the age of onset toward gradually younger people. IBD represents a genuine problem in public health because of the absence of etiologic treatment. The clinical image is characterized by recurrent segmental or total inflammatory involvement of the large and/or small intestine, often resulting in a chronic, unpredictable course. The symptoms of both are extremely unpleasant and impact all aspects of quality of life. They include diarrhea, abdominal pain, rectal bleeding, fever, nausea, weight loss, lethargy, and loss of appetite. If left untreated, malnutrition, dehydration, and anemia follow, which, in extreme cases, can even lead to death. Although many patients are managed successfully with conventional medical therapy, such as anti-inflammatory corticosteroid treatment, some stay refractory to treatment, most will have recurrent activity of disease, and two thirds will require surgery. Administered orally or by injection, only a fraction of the active components of most conventional drugs reaches the intended target site, the inflamed intestinal lining. This is not only an inefficient way to deliver drugs, but, more important, means that patients are often subject to a spectrum of unpleasant side effects that result from the high levels of the drugs in other, otherwise healthy tissues and organs of the body. Lothar Steidler Copyright © 2001 Lothar Steidler. All rights reserved. Recurrent Lower Abdominal Pain in Older Children and Adolescents: Revised Clinical Approach Mon, 01 Jan 1900 00:00:00 +0000 Pelvic and lower abdominal pain constitutes more than 30% of the referrals to our adolescent medicine and gastroenterology clinics. These cases are responsible for numerous school absences and significant cost to the healthcare system. This article will review the most common causes of lower abdominal and pelvic pain in adolescents, diagnostic and management issues, as well as prevention. Harohalli Shashidhar and Hatim A. Omar Copyright © 2005 Harohalli Shashidhar and Hatim A. Omar. All rights reserved. Narrow-Band Imaging in Digestive Endoscopy Mon, 01 Jan 1900 00:00:00 +0000 The application of opto-electronics in video-endoscopes improves the accuracy in diagnosis, through image processing and digital technology. Narrow Band Imaging (NBI), consists of using interference filters for the illumination of the target in narrowed blue and green bands of the spectrum. NBI is combined with magnifying endoscopy using an objective macro or an optical zoom. The NBI technique developed by Olympus Medical Systems is now available in the most recent models of video-endoscopes that use the non-sequential system of illumination (Lucera Spectrum) or the sequential R/G/B system of illumination (Exera II). The major contribution of the technique is in the characterization (analysis after detection) of the flat and superficial neoplastic areas of the digestive mucosa, with a specific application to the identification of intestinal metaplasia and early neoplastic changes in the Barrett's esophagus. The technique also proves helpful for the assessment of the vascular pattern in chronic inflammatory disorders of the digestive mucosa. R. Lambert, K. Kuznetsov, and J-F. Rey Copyright © 2007 R. Lambert et al. All rights reserved. Liver Abscess due to Sewing Needle Perforation Mon, 01 Jan 1900 00:00:00 +0000 Ewoud H. Jutte and Huib A. Cense Copyright © 2010 Ewoud H. Jutte and Huib A. Cense. All rights reserved. The Production of the Oral Mucosa of Antiendomysial and Anti—Tissue-Transglutaminase Antibodies in Patients with Celiac Disease: A Review Mon, 01 Jan 1900 00:00:00 +0000 Celiac disease (CD) is a lifelong, T cell—mediated enteropathy, triggered by the ingestion of gluten and related prolamins in genetically susceptible subjects, resulting in minor intestinal mucosal injury, including villous atrophy with crypt hyperplasia and intraepithelial lymphocytosis, and subsequent nutrient malabsorption. Although serological tests for antiendomysial (EMA) and anti—tissue transglutaminase (anti-tTG) autoantibodies are used to screen and follow up on patients with CD, diagnostic confirmation is still based on the histological examination of the small intestinal mucosa. Although the small intestinal mucosa is the main site of the gut involved in CD, other mucosal surfaces (such as gastric, rectal, ileal, and esophageal) belonging to the gastrointestinal tract and the gut-associated lymphoid tissue (GALT) can also be involved. A site that could be studied less invasively is the mouth, as it is the first part of the gastrointestinal system and a part of the GALT. Indeed, not only have various oral ailments been reported as possible atypical aspects of CD, but it has been also demonstrated that inflammatory changes occur after oral supramucosal application and a submucosal injection of gliadin into the oral mucosa of CD patients. However, to date, only two studies have assessed the capacity of the oral mucosa of untreated CD patients to EMA and anti-tTG antibodies. In this paper, we will review studies that evaluate the capacity of the oral mucosa to produce specific CD autoantibodies. Discrepancies in sensitivity from the two studies have revealed that biopsy is still not an adequate procedure for the routine diagnostic purposes of CD patients, and a more in-depth evaluation on a larger sample size with standardized collection and analysis methods is merited. However, the demonstration of immunological reactivity to the gluten ingestion of the oral mucosa of CD, in terms of IgA EMA and anti-tTG production, needs to be further evaluated in order to verify whether the oral mucosa is colonized by lymphocytes activated in the intestine or if gluten could stimulate naïve lymphocytes directly in the oral mucosa. This would have important implications for the pathogenesis, diagnosis, and treatment of CD. Domenico Compilato, Giuseppina Campisi, Luca Pastore, and Antonio Carroccio Copyright © 2010 Domenico Compilato et al. All rights reserved. Molecular Biology of Rotavirus Entry and Replication Mon, 01 Jan 1900 00:00:00 +0000 Rotavirus is a nonenveloped, double-stranded, RNA virus belonging to the Reoviridae family and is the major etiological agent of viral gastroenteritis in young children and young animals. Remarkable progress in the understanding of the rotavirus cycle has been made in the last 10 years. The knowledge of viral replication thus far acquired is based on structural studies, the expression and coexpression of individual viral proteins, silencing of individual genes by siRNAs, and the effects that these manipulations have on the physiology of the infected cell. The functions of the individual rotavirus proteins have been largely dissected; however, the interactions between them and with cell proteins, and the molecular mechanisms of virus replication, are just beginning to be understood. These advancements represent the basis for the development of effective vaccination and rational therapeutic strategies to combat rotavirus infection and diarrhea syndromes. In this paper, we review and try to integrate the new knowledge about rotavirus entry, replication, and assembly, and pose some of the questions that remain to be solved. Marie Christine Ruiz, Theresa Leon, Yuleima Diaz, and Fabian Michelangeli Copyright © 2009 Marie Christine Ruiz et al. All rights reserved. Incidental Discovery of Emphysematous Cystitis with Rapid Resolution in a Patient Presenting with Acute Pancreatitis Mon, 01 Jan 1900 00:00:00 +0000 M. Al-Assiri and P. Chan Copyright © 2004 M. Al-Assiri and P. Chan. All rights reserved.