Saudi Journal of Gastroenterology
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   2016| January-February  | Volume 22 | Issue 1  
    Online since January 12, 2016

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The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models
Ioana Miruna Balmus, Alin Ciobica, Anca Trifan, Carol Stanciu
January-February 2016, 22(1):3-17
DOI:10.4103/1319-3767.173753  PMID:26831601
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patient's immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.
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Effect of telmisartan on histological activity and fibrosis of non-alcoholic steatohepatitis: A 1-year randomized control trial
Shahinul Alam, Jahangir Kabir, Golam Mustafa, UtpalDas Gupta, SKMNazmul Hasan, AKMKhorshed Alam
January-February 2016, 22(1):69-76
DOI:10.4103/1319-3767.173762  PMID:26831610
Background/Aim:   Telmisartan can attenuate two hit pathogenesis of non-alcoholic steatohepatitis (NASH). This study aimed to observe the effect of Telmisartan on non-alcoholic fatty liver disease (NAFLD) activity score (NAS) and fibrosis score in NASH patients. Patients and Methods: A total of 50 NASH patients were randomized; 35 of group 1 were treated with Telmisartan 40/80 mg once daily with life style modification (TL) and 15 of group 2 underwent only life style modification (L) for 1 year. At the end, 20 of TL group and 10 of L group were analyzed. Those who showed NAS improvement ≥ 2 or NAS improvement ≥ 1 with fibrosis improvement ≥ 1 were considered as responders. Results: Baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance index, components of metabolic syndrome, age, and sex were similar in both groups. At the end of study, NAS improvement in TL and L groups was 2.15 ± 1.66 and 1.10 ± 0.57 (P = 0.017) and fibrosis improvement was 0.65 ± 0.93 and -0.30 ± 0.48 (P = 0.001), respectively. NAS improved by ≥ 2 in 13 (65%) and 2 (20%) patients and fibrosis score improved by ≥ 1 in 8 (40%) patients and none of the patients in TL group and L group, respectively. Telmisartan and life style modification could improve steatosis, ballooning, lobular inflammation, and fibrosis. Life style modification could improve ballooning only, but fibrosis deteriorated. TL group showed improvement in NAS and fibrosis score [P value: 0.035; odds ratio (OR) =92.07, confidence interval (CI) =1.39-6106] to the level of response by regression analysis. Weight reduction and improvement of metabolic syndrome did not influence the response. There were similar minor adverse events in both groups. Conclusion: Telmisartan improved NAS and fibrosis score in NASH with insignificant adverse events.
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Healing acceleration of acetic acid-induced colitis by marigold (Calendula officinalis) in male rats
Nader Tanideh, Akram Jamshidzadeh, Masood Sepehrimanesh, Masood Hosseinzadeh, Omid Koohi-Hosseinabadi, Asma Najibi, Mozhdeh Raam, Sajad Daneshi, Seyedeh-Leili Asadi-Yousefabad
January-February 2016, 22(1):50-56
DOI:10.4103/1319-3767.173759  PMID:26831607
Background/Aim: Ulcerative colitis (UC) is a type of chronic inflammatory bowel disease with unknown etiology. Several therapeutic strategies such as consumption of medicinal plants have been used for its treatment. The aim of this study was to evaluate healing effects of Calendula officinalis hydroalcoholic extract in experimentally induced UC in rat. Materials and Methods: Ninety-six rats, weighing 200 ± 20 g, were randomly divided into eight equal groups. UC induced by 3% acetic acid and oral doses of C. officinalis extract, 1500 and 3000 mg/kg, and enema (gel 10% and 20%) were given. Two groups as positive controls were given asacol (enema) and oral mesalamine. Negative control groups were given normal saline and base gel. On days 3 and 7, intestinal histopathology and weight changes, plus oxidative stress indices including malondialdehyde (MDA) level and myeloperoxidase (MPO) activity were assayed. Results: A significant increase in the body weight of rats was seen in the group given C. officinalis extract 3000 mg/kg orally, oral mesalamine, and 20% intracolonic gel form of marigold extract compared with negative control and base gel groups during the experimental period. Acute inflammation and granular atrophy after UC induction were resolved completely completely by both 20% intracolonic gel and 3000 mg/kg orally. An increase in MPO activity and a decrease in MDA level in response to oral and intracolonic gel form of C. officinalis were observed 3 and and 7 days after treatment (P < 0.05). Conclusion: Our results indicate that oral and enema forms of hydroalcoholic extract of C. officinalis can be offered as are potential therapeutic agents for UC induced in rats.
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MicroRNA-155-enhanced autophagy in human gastric epithelial cell in response to Helicobacter pylori
Kai Wu, Chaohui Zhu, Yi Yao, Xin Wang, Jiugang Song, Junshan Zhai
January-February 2016, 22(1):30-36
DOI:10.4103/1319-3767.173756  PMID:26831604
Background/Aim: MicroRNAs (miRNAs) are a class of small noncoding RNAs acting as posttranscriptional gene expression regulators in many physiological and pathological conditions. MiR-155 is one kind of miRNAs that plays an important role in causing various diseases. However, the precise molecular mechanism of the ectopic expression of miR-155 in Helicobacter pylori infection remains poorly understood. Autophagy has recently been identified as an effective way to control the intracellular bacterium survival. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-H. pylori response. Patients and Methods: Totally 86 H. pylori-positive patients together with 10 H. pylori-negative, healthy control subjects were included in the study. Correlation between immunohistochemical grades and miR-155 expression were determined. Molecular mechanism of miR-155 on regulation of autophagy and elimination of intracellular H. pylori were determined using the GES-1 cell model. Results: We found that overexpression of miR-155 by transfecting miR-155 mimics could significantly decrease the survival of intracellular H. pylori, and this process was through induction of autophagy. Furthermore, there was a significant correlation between miR-155 and immunohistochemical grades in H. pylori-positive patients, and miR-155 expression were decreased in the intestinal metaplasia group. Conclusions: The results have indicated that the miR-155 expression level plays a key role in immunity response against H. pylori and this might provide potential targets for the future treatment of H. pylori-related diseases.
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Carbon dioxide insufflation or warm-water infusion for unsedated colonoscopy: A randomized controlled trial in patients with chronic constipation in China
Xiaoling Xu, Haihang Zhu, Di Chen, Langui Fan, Ting Lu, Qin Shen, Chaowu Chen, Denghao Deng
January-February 2016, 22(1):18-24
DOI:10.4103/1319-3767.173754  PMID:26831602
Aims: The effect of carbon dioxide (CO 2 ) insufflation and warm-water infusion during colonoscopy on patients with chronic constipation remains unknown. We evaluated CO 2 insufflation and warm-water irrigation versus air insufflation in unsedated patients with chronic constipation in China. Patients and Methods: This randomized, single-center, controlled trial enrolled 287 consecutive patients, from January 2014 to January 2015, who underwent colonoscopy for chronic constipation. Patients were randomized to CO 2 insufflation, warm-water irrigation and air insufflation colonoscopy insertion phase groups. Pain scores were assessed by the visual analog scale (VAS). The primary outcome was real-time maximum insertion pain, recorded by an unblinded nurse assistant. At discharge, the recalled maximum insertion pain was recorded. Meanwhile, patients were requested to select the VAS at 0, 10, 30, and 60 min after the procedure. In addition, cecal intubation and withdrawal time, total procedure time, and adjunct measures were recorded. Results: A total of 287 patients were randomized. The correlation between real-time and recalled maximum insertion pain ((Pearson coefficient r = 0.929; P < 0.0001) confirmed internal validation of the primary outcome. The mean real-time maximum pain scores during insertion 2.9 ± 2.1 for CO 2 , 2.7 ± 1.9 for water achieved a significantly lower pain score compared with air (5.7 ± 2.5) group (air vs CO 2 P < 0.001; air vs water P < 0.001). However, no significant pain score differences were found between the patients in the CO 2 and water groups (CO 2 vs water, P = 0.0535). P values in painless colonoscopy and only discomfort colonoscopy (pain 1-2) were, respectively, 6 (6.4%) and 8 (8.5%) for air; 17 (17.7%) and 29 (30.2%) for CO 2 ; 16 (16.5%) and 31 (31.9%) for water. At 0, 10, 30, and 60 min postprocedure, pain scores showed in the CO 2 and water groups had significantly reduced than in air group. Insertion time was significantly different between air (10.6 ± 2.5) and CO 2 ( 7.2 ± 1.4) (air vs CO 2 P < 0.001), air and water (6.9 ± 1.3) (air vs water P < 0.001). However, CO 2 and was not significantly different in cecum-intubated time (CO 2 vs water, P = 0.404). CO 2 and water group in extubation time were significantly different, respectively, CO 2 (7.9 ± 1.1) and water (8.0 ± 1.1) (CO 2 vs water, P = 0.707). CO 2 or water group required less implementation of adjunct measures and more willingness to repeat the procedure. Conclusions: Compared with air, the CO 2 or water-aided method reduced real-time maximum pain and cecum-intubated time for chronic constipated patients in unsedated colonoscopy. The CO 2 insufflation or warm-water irrigation may be a simple and inexpensive way to reduce discomfort in unsedated patients with constipation. This study demonstrated an advantage of using CO 2 insufflation and warm-water irrigation during colonoscopy in unsedated constipated patients in China.
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Noninvasive fibrosis marker can predict recurrence of hepatocellular carcinoma after radiofrequency ablation
Hyun Ah Chung, Jeong-Han Kim, Young Hwang, Hong Seok Choi, Soon Young Ko, Won Hyeok Choe, So Young Kwon
January-February 2016, 22(1):57-63
DOI:10.4103/1319-3767.173760  PMID:26831608
Background/Aims: Tumor recurrence after curative therapy is common for patients with hepatocellular carcinoma (HCC). As fibrosis and chronic inflammation contribute to the progression of HCC, we aimed to identify the predictive value of inflammatory and fibrosis markers for HCC recurrence after curative therapy using radiofrequency ablation (RFA). Materials and Methods: We retrospectively reviewed the records of patients with HCC treated with RFA between October 2005 and September 2013. The median duration of follow-up was 40 months (4-95 months). Inflammatory and fibrosis markers and demographic and clinical data were analyzed by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis. Results: A total of 98 patients were included for analysis. There were 54 cases of HCC recurrence (55.1%). The aspartate aminotransferase-to-platelet ratio index (APRI; 2.3 ± 1.8 vs. 1.3 ± 1.4, P = 0.018) was significantly higher in the recurrence group than in the recurrence-free group. In multivariate analysis, APRI (hazard ratio, 2.64; confidence interval, 1.488-4.714; P = 0.001) was an independent risk factor for tumor recurrence. In particular, patients with APRI >1.38 showed a higher recurrence rate than patients with APRI ≤1.38 (P < 0.001). Longitudinal analysis showed persistently higher APRI values when assessed 12 months after RFA in patients who developed recurrence during follow-up than those who remained recurrence-free. Conclusions: These findings show that a high APRI value is associated with HCC recurrence after RFA. Therefore, APRI could play an important role in predicting HCC recurrence after RFA.
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Predictors of incomplete optical colonoscopy using computed tomographic colonography
Reetika Sachdeva, Salina D Tsai, Mohamad H El Zein, Alan A Tieu, Ahmed Abdelgelil, Sepideh Besharati, Mouen A Khashab, Anthony N Kalloo, Vivek Kumbhari
January-February 2016, 22(1):43-49
DOI:10.4103/1319-3767.173758  PMID:26831606
Background/Aims: Optical colonoscopy (OC) is the primary modality for investigation of colonic pathology. Although there is data on demographic factors for incomplete OC, paucity of data exists for anatomic variables that are associated with an incomplete OC. These anatomic variables can be visualized using computed tomographic colonography (CTC). We aim to retrospectively identify variables associated with incomplete OC using CTC and develop a scoring method to predict the outcome of OC. Patients and Methods: In this case-control study, 70 cases ( with incomplete OC) and 70 controls (with complete OC) were identified. CTC images of cases and controls were independently reviewed by a single CTC radiologist. Demographic and anatomical parameters were recorded. Data was examined using descriptive linear statistics and multivariate logistic regression model. Results: On analysis, female gender (80% vs 58.6% P = 0.007), prior abdominal/pelvic surgeries (51.4% vs 14.3% P < 0.001), colonic length (187.6 ± 30.0 cm vs 163.8 ± 27.2 cm P < 0.001), and number of flexures (11.4 ± 3.1 vs 8.4 ± 2.9 P < 0.001) increased the risk for incomplete OC. No significant association was observed for increasing age (P = 0.881) and history of severe diverticulosis (P = 0.867) with incomplete OC. A scoring system to predict the outcome of OC is proposed based on CTC findings. Conclusion: Female gender, prior surgery, and increasing colonic length and tortuosity were associated with incomplete OC, whereas increasing age and history of severe diverticulosis were not. These factors may be used in the future to predict those patients who are at risk of incomplete OC.
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The prognostic value of UHRF-1 and p53 in gastric cancer
Nalan A Babacan, Hatice Reyhan Egilmez, Birsen Yücel, Parlak Ilknur, Mehmet Metin Seker, Turgut Kaçan, Aykut Bahçeci, Sener Cihan, Bülent Akinci, Berna Eriten, Saadettin Kiliçkap
January-February 2016, 22(1):25-29
DOI:10.4103/1319-3767.173755  PMID:26831603
Background/Aims: This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. Patients and Methods: Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. Results: The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and fi ve (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1-110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132). Conclusion: According to this study, UHRF-1and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differantiating between gastric cancer and gastritis.
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CO 2 insufflation or warm water infusion for unsedated colonoscopy: A randomized controlled trial in patients with chronic constipation in China
Sharmila Subramaniam, Kesavan Kandiah, Pradeep Bhandari
January-February 2016, 22(1):1-2
DOI:10.4103/1319-3767.173752  PMID:26831600
  2,288 417 -
Antiviral efficacy of entecavir versus entecavir plus adefovir for hepatitis B virus rtA181V/T mutants alone
Myung Jin Oh, Heon Ju Lee
January-February 2016, 22(1):37-42
DOI:10.4103/1319-3767.173757  PMID:26831605
Background/Aims: Hepatitis B virus (HBV) rtA181V/T mutants developed by long-term nucleos(t) ide analogue therapy are known to present cross-resistance for other nucleos (t) ide analogues, except entecavir (ETV). Some studies reported that HBV rtA181V/T mutants could induce cross-resistance to ETV and showed incomplete response as well as persistence of HBV DNA, despite rescue therapy by ETV. This study aimed to investigate the antiviral efficacy of ETV monotherapy and ETV plus adefovir (ADV) as rescue therapy for HBV rtA181V/T single mutation. Patients and Methods: A total of 30 patients who received ETV alone (1.0 mg/day, n = 16) or ETV plus ADV (10.0 mg/day, n = 14) over 48 weeks between April 2008 and October 2011 were enrolled. Virological, biochemical, and serological response at 48 weeks of rescue therapy were investigated retrospectively. Results: No significant difference in baseline characteristics was observed between the ETV group and the ETV plus ADV group. Virological response showed complete response (62.5 vs. 42.9%), partial response (6.3 vs. 28.6%), non-response (25.0 vs. 28.6%), and virological breakthrough (6.3 vs. 0%) in the two groups, respectively. Virological response did not statistically differ between both groups (P = 0.278). No significant difference in the mean reduction of serum HBV DNA and biochemical response was observed between both groups (4.3 ± 2.9 vs. 4.1 ± 1.8 log 10 IU/ml; P = 0.294 and 88.9 vs. 100%; P = 1.000, respectively). In addition, no significant difference in HBeAg loss or seroconversion was observed between the two groups (26.7 vs. 28.6%; P = 1.000). Conclusions: ETV monotherapy and ETV plus ADV therapy were clinically effective and comparable as rescue therapy for HBV rtA181V/T mutants alone.
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Factors influencing challenging colonoscopies during anesthesiologist-assisted deep sedation
Fabrizio Cardin, Nadia Minicuci, Alessandra Andreotti, Elisa Granziera, Carmelo Militello
January-February 2016, 22(1):64-68
DOI:10.4103/1319-3767.173761  PMID:26831609
Background/Aim: Increased demand for colon cancer screening procedures can significantly impact on routine colonoscopy management at dedicated facilities, prompting a review of the factors that can negatively affect workflow. Although potential adverse effects and impact on costs of deep sedation have been documented elsewhere, this study focuses on variables that can influence performance of colonoscopy in deep sedation and interfere with normal procedure scheduling in settings where the presence of an anesthesiologist is mandatory. Patients and Methods: We performed a cross-sectional study of the activities of a colonoscopy screening unit, applying Bayesian Network (BN) analysis, designed to assess interdependencies among variables that can affect a process in complex, multidimensional systems. The study was performed at a teaching hospital where endoscopists and anesthesiologists of varying work experience operate on a rota basis. During a six-month period, we analyzed 1485 consecutive colonoscopies performed under deep propofol sedation, administered by an anesthesiologist via hand-controlled syringe. The BN was constructed with the variables: Gender, age, ASA status, bowel preparation, baseline blood pressure, endoscopist's experience, anesthesiologist's experience, presence of polypectomy, and the target node, "challenging procedure." This previously undefined category refers to any events disrupting the scheduled rota. Result and Conclusion: Two distinct networks were identified. One deals mainly with relationships among the variables, patients' demographic and clinical characteristics (procedures with polypectomy, ASA and baseline blood pressure). The other explains relationships among the variables, "challenging procedure," bowel preparation, and endoscopist's experience. The factors associated with the anesthesiologist's activity do not influence challenging colonoscopies.
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A prospective trial in Saudi Arabia comparing the 14-day standard triple therapy with the 10-day sequential therapy for treatment of Helicobacter pylori infection: A further confirmation of "Geographic Weight"
Giuseppe Losurdo, Andrea Iannone, Floriana Giorgio, Enzo Ierardi, Alfredo Di Leo, Mariabeatrice Principi
January-February 2016, 22(1):77-78
DOI:10.4103/1319-3767.173763  PMID:26831611
  1,839 263 -
Updated Helicobacter pylori management in 2015
Amin Talebi Bezmin Abadi
January-February 2016, 22(1):80-80
DOI:10.4103/1319-3767.173765  PMID:26831613
  1,633 231 -
Response to: Treatment prolongation or quadruple therapy:- Individualization by geographical region
Fahad Alsohaibani, Hamad Al Ashgar, Khalid Al Kahtani, Musthafa Peedikayil, Abdulrahman Alfadda, Mohammed Q Khan, Ingvar Kageri
January-February 2016, 22(1):79-79
DOI:10.4103/1319-3767.173764  PMID:26831612
  1,587 235 -
Prevalence of celiac disease in Saudi children: Is it underestimated?
Mahmood Dhahir Al-Mendalawi
January-February 2016, 22(1):83-83
DOI:10.4103/1319-3767.173768  PMID:26831616
  1,586 227 -
Celiac disease among symptom-free children-more than what is expected
Majid A Almadi, Abdulrahman M Aljebreen
January-February 2016, 22(1):82-82
DOI:10.4103/1319-3767.173767  PMID:26831615
  1,587 216 -
Response to: Serum paraoxonase and malondialdehyde levels in asymptomatic cholelithiasis
Aytaç Atamer, Yildiz Atamer, Ahmet S Can
January-February 2016, 22(1):84-85
DOI:10.4103/1319-3767.173769  PMID:26831617
  1,561 186 -
Response to: Reply on "Renewed Helicobacter pylori management and therapy in 2015"
Sharmila Fagoonee, Rinaldo Pellicano
January-February 2016, 22(1):81-81
DOI:10.4103/1319-3767.173766  PMID:26831614
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