Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis.

OBJECTIVE: This study was designed to identify the effect of rivaroxaban, a direct factor Xa inhibitor, on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. MATERIALS AND METHODS: Twenty-four female Wistar rats were divided into 4 groups of 6 each. Group 1 received TNBS + rivaroxaban, group 2 received TNBS + methylprednisolone, group 3 received TNBS and group 4 received a saline enema. Colitis was induced in the rats by the intracolonic administration of TNBS. Rivaroxaban and methylprednisolone were given by oral gavage daily for 7 days. The rats were killed 7 days after the induction of colitis. RESULTS: Rivaroxaban and methylprednisolone significantly reduced gross damage and histopathological scores. Rivaroxaban was more effective than methylprednisolone in terms of microscopic mucosal healing. Rivaroxaban attenuated the accumulation of malonyldialdehyde (MDA) and transforming growth-factor ß1 (TGF-ß1) and the activities of myeloperoxidase (MPO), matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1. Methylprednisolone reduced only the activity of MPO and the accumulation of MDA and TGF-ß1. Superoxide dismutase activity showed a restoration to normal levels after rivaroxaban and methylprednisolone administration. CONCLUSIONS: Rivaroxaban showed a therapeutic effect in the TNBS model of experimental colitis, and it seemed to be at least as effective as methylprednisolone. This effect may be brought about by the inhibition of oxidative stress and metalloproteinase activity associated with tissue injury and remodeling.

The impact of anorectal biofeedback therapy on the quality of life of patients with dyssynergic defecation.

BACKGROUND/AIMS: Dyssynergic defecation is a common health problem affecting the quality of life of patients adversely. We aimed to evaluate the impact of biofeedback therapy on the quality of life of constipated patients due to dyssynergic defecation. MATERIALS AND METHODS: Constipated patients due to dyssynergic defecation were enrolled to the study. Patients having secondary causes of constipation and who didn't fulfill the eligible criteria were excluded. All the patients underwent three to ten sessions each of which was thirty minutes biofeedback therapy under the supervision of a trained nurse. After one month the patients were assessed for the control. The impact of biofeedback therapy on the quality of life of patients having dyssynergic defecation was assessed using the validated Medical Outcomes Study Short Form-36 (SF-36) questionnaire before and one month after therapy. RESULTS: Thirty-two patients (20 female 62.5%, 12 male 37.5% and mean age 48 (18-72) underwent three to ten sessions biofeedback therapy. Post-therapy improvements of subscores of SF-36 consists of eight domains were all statistically significant when we compared with the pre-therapy values. CONCLUSION: This study showed not only the effectiveness of biofeedback as a therapy modality for constipation but also its impact on the improvement of QOL of constipated patients due to dyssynergic defecation. Patients with chronic constipation not improved by dietary fiber and laxatives should be referred to specialized centers that have facilities for further anorectal physiological assessments.

Pancreatic metastasis in a case of small cell lung carcinoma diagnosed by EUS.

Small-cell lung carcinoma represents a group of highly malignant tumors characterized by early and widespread metastais even at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm. A 57-year-old patient was admitted with an intense cough and complaints of abdominal discomfort. A chest X-Ray showed no evidence of lung mass but did show signs of lymphadenopathy. In addition, there was little evidence for malignancy based on a transbronchial needle aspiration. In contrast, there was a mass in the head portion of the pancreas. We diagnosed a case of small-cell lung carcinoma metastasis in the pancreas by using an endoscopic ultrasound-guided fine-needle aspiration biopsy. This case demonstrates that endoscopic ultrasound-guided fine-needle aspiration biopsy is an important tool in the diagnosis of metastatic pancreatic neoplasms.

The role of interleukin-1 gene polymorphisms and Helicobacter pylori in gastroesophageal reflux disease.

BACKGROUND/AIMS: Our aim is to assess the relationship between interleukin 1ß (IL-1 ß), (-511,-31 alleles), interleukin 1RN (IL-RN), Helicobacter pylori (HP) status and gastroesophageal reflux disease (GERD) diagnosed by pH monitoring in the Turkish population. MATERIALS AND METHODS: A Total of 100 consecutive patients with GERD were enrolled in the study. Genotypes of IL-1ß (-511,-31), IL-1RN gene polymorphisms and HP status of the patients were analyzed. RESULTS: While thirty-two patients were diagnosed as esophagitis with varying severity the remaining patients had no esophagitis. Seventy six participants were positive for HP and the remaining patients were negative. The difference between erosive and non-erosive groups was statistically significant when we compared IL-1ß (-511) but no difference regarding IL-1ß (-31) and IL-1RN variations. We also analyzed T/T, C/T and C/C alleles and the difference was significant statistically in T/T allele between patients with and without erosive GERD 1 (3.1%) vs. 12 (17.9%), respectively with a p value<0.05. But C/C, C/T alleles of (-511), (-31) and IL-1RN polymorphisms were not statistically significant between the groups. CONCLUSION: IL-1ß genetic polymorphisms may take part in the pathophysiology of gastroesophageal reflux disease.

Comparison of double balloon enteroscopy in adults and children.

AIM: To compare results of double balloon enteroscopy (DBE) procedures in pediatric and adult patients. METHODS: The medical files of patients who underwent DBE at Gazi University School of Medicine, Ankara, Turkey between 2009 and 2011 were examined retrospectively. Adult and pediatric patients were compared according to DBE indications, procedure duration, final diagnosis, and complications. DBE procedures were performed in an operating room under general anesthesia by two endoscopists. An oral or anal approach was preferred according to estimated lesion sites. Overnight fasting of at least 6 h prior to the start of the procedure was adequate for preprocedural preparation of oral DBE procedures. Bowel cleansing was performed by oral administration of sennosides A and B solution, 2 mL/kg, and anal saline laxative enema. The patients were followed up for 2 h after the procedure in terms of possible complications. RESULTS: DBE was performed in 35 patients (5 pediatric and 30 adult). DBE procedures were performed for abdominal pain, chronic diarrhea, bleeding, chronic vomiting, anemia, and postoperative evaluation of anastomosis. Final diagnosis was diffuse gastric angiodysplasia (n = 1); diffuse jejunal angiodysplasia (n = 1); ulceration in the bulbus (n = 1); celiac disease (n = 1); low differentiated metastatic carcinoma (n = 1); Peutz-Jeghers syndrome (n = 1); adenomatous polyp (n = 1) and stricture formation in anastomosis line (n = 1). During postprocedural follow-up, abdominal pain and elevated amylase levels were noted in three patients and one patient developed abdominal perforation. CONCLUSION: With the help of technological improvements, we may use enteroscopy as a safe modality more frequently in younger and smaller children.

Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis.

BACKGROUND AND AIMS: After NADPH oxidase mediated radical formation, hypochloric acid (HOCl) is formed when Cl is used as a substrate by the myeloperoxidase enzyme. Myeloperoxidase is secreted from H2O2 activated leukocytes with polymorphic nuclei. The generation of HOCl also causes the formation of advanced oxidation protein products (AOPP) through damage to normal tissue and protein oxidation. AOPP has been identified as a marker of inflammation in many diseases. However, AOPP has not been investigated in ulcerative colitis. As a result of mucosal inflammation in ulcerative colitis, oxidative stress can occur. We aimed to determine whether plasma AOPP and oxidative stress markers are detectable in active ulcerative colitis. METHODS: The patient group consisted of 59 patients who were diagnosed with ulcerative colitis in the clinic by histology and endoscopy. The patients were hospitalised and treated in the Gastroenterology Department of Gazi University Medical Facility. The 59 patients were separated into active and inactive groups according to the endoscopic activation index (EAI). Group I consisted of 33 active ulcerative colitis patients, Group II consisted of 26 inactive ulcerative colitis patients and Group III consisted of healthy control subjects. The disease activity of these patients were measured using the Rachmilewitz EAI based on rectosigmoidoscopic or colonoscopic findings. Patients with EAI scores greater than 4 were scored as having active disease (Group I). Patients with EAI<4 were scored as being in disease remission (Group II). The control subjects (Group III) were 51 healthy individuals. The plasma AOPP levels were measured using a spectrophotometric method. RESULTS: There were no statistically significant differences in gender (P<0.22) and age (P<0.11) between the groups examined. The plasma AOPP level in Group I was 148.72±9.08µmol/L. The plasma AOPP level in Group II was 74.48±7.06µmol/L, and the plasma AOPP level in Group III was 64.93±2.55µmol/L. The AOPP levels in Group I were statistically different than in Group II and III (P<0.05). The AOPP levels were similar between Group II and Group III (P>0.05). The EAI value was 8.84±0.31 in Group I and 2.76±0.08 in Group II. There were statistically significant differences for EAI between groups (P<0.05). The correlation between AOPP and EAI in all patients with ulcerative colitis were statistically significant (P<0.05, r=0.61). The regression model in this correlation was statistically significant (y=49.68+10.75x, P<0.05). DISCUSSION: Based on our results, we suggest that AOPP could be used as a non invasive activation marker for ulcerative colitis patients.

Ineffective esophageal motility and gastroesophageal reflux disease: a close relationship?

BACKGROUND/AIMS: An association between ineffective esophageal motility and gastroesophageal reflux disease is already known, but there are also some conflicting data. We evaluated the association between ineffective esophageal motility and gastroesophageal reflux disease in patients who underwent ambulatory pH monitoring for the evaluation of reflux symptoms at Gazi University, Gastroenterology Clinic. MATERIALS AND METHODS: A total of 239 patients who underwent endoscopy, esophageal manometry and ambulatory 24-h pH monitoring due to reflux symptoms were enrolled. Of them, we selected patients who had normal esophageal motility and ineffective esophageal motility. The endoscopy and ambulatory pH monitoring findings were compared between the two groups. RESULTS: Of the 239 patients who presented with reflux symptoms, pathologic acid reflux or endoscopic esophagitis was found in 114 (48%). Ineffective esophageal motility was found in 18 (16%) in the pathologic reflux group and in 4 (3%) in the functional reflux group (p=0.01). Ambulatory pH, manometric and demographic findings were compared in ineffective esophageal motility and normal motility groups. Lower esophageal sphincter (LES) pressures were lower in the ineffective esophageal motility group (19.7 versus 16.2; p=0.01), and total reflux times in both supine and upright position were higher (10.3 versus 4.9; p=0.01) inthe ineffective esophageal motility group. Ineffective esophageal motility patients were older and more obese than normal motility group patients. CONCLUSIONS: This study points to a clear association between ineffective esophageal motility and gastroesophageal reflux disease as defined by ambulatory pH monitoring.

The role of oxidative DNA damage, DNA repair, GSTM1, SOD2 and OGG1 polymorphisms in individual susceptibility to Barrett's esophagus.

Determination of the genetic alterations, which play a role in the etiology of Barrett's esophagus (BE), could help identify high-risk individuals for esophageal adenocarcinoma (EA). The aim of the present study was to investigate the role of oxidative DNA damage, glutathione (GSH) concentration as oxidative stress parameters and DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms as individual susceptibility parameters in the etiology of BE. The study groups comprised BE patients who were clinically diagnosed (n = 40) and a healthy control group (n = 40). Basal DNA damage, pyrimidine and purine base damage after H(2)O(2) induction, H( 2)O(2) sensitivity, DNA repair capacity, oxidized pyrimidine and purine base damage repair were evaluated in peripheral blood lymphocytes with a modified comet assay using specific endonucleases (Endo III and Fpg). Polymerase chain reaction-restriction length polymorphism (PCR-RFLP)-based assays were used for genotyping. The patient group showed elevated levels of basal DNA damage, pyrimidine base damage and H(2)O(2) sensitivity as compared to controls (p < .05). DNA repair capacity, oxidized pyrimidine and purine base damage repair capacity, were not statistically different between patients and controls. GSH concentration was found to be significantly lower in smoking patients than in the controls (p < .05). None of the genetic variations changed the risk of having BE disease. However, patients carrying the variant OGG1 Cys allele showed elevated levels of pyrimidine base damage as compared to patients carrying the wild-type OGG1 Ser (p < .05). The results of this study point to a role of oxidative DNA damage in BE. However, DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic polymorphisms appeared to play no role in the individual susceptibility to this disease.

Is there an association between Helicobacter pylori in the inlet patch and globus sensation?

AIM: To determine the association between Helicobacter pylori (H. pylori) and globus sensation (GS) in the patients with cervical inlet patch. METHODS: Sixty-eight patients with esophageal inlet patches were identified from 6760 consecutive patients undergoing upper gastrointestinal endoscopy prospectively. In these 68 patients with cervical inlet patches, symptoms of globus sensation (lump in the throat), hoarseness, sore throat, frequent clearing of the throat, cough, dysphagia, odynophagia of at least 3 mo duration was questioned prior to endoscopy. RESULTS: Cervical heterotopic gastric mucosa (CHGM) was found in 68 of 6760 patients. The endoscopic prevalence of CHGM was determined to be 1%. H. pylori was identified in 16 (23.5%) of 68 patients with inlet patch. Fifty-three patients were classified as CHGM II. This group included 48 patients with globus sensation, 4 patients with chronic cough and 1 patient with hoarseness. All the patients who were H. pylori (+) in cervical inlet patches had globus sensation. CONCLUSION: Often patients with CHGM have a long history of troublesome throat symptoms. We speculate that disturbances in globus sensation are like non-ulcer dyspepsia.

Cerebral sinus thrombosis in a patient with active ulcerative colitis and double heterozygosity for Factor V Leiden and prothrombin gene mutations.

Inflammatory bowel diseases are associated with increased risk for thrombotic complications, In patients with ulcerative colitis (UC) cerebral sinus venous thrombosis (CSVT) is an extremely rare complication. We report a patient with active UC and CSVT. The patient was heterozygous for Factor V Leiden and G20210A prothrombin gene mutations without other identifiable precipitating factors. This patient highlights the need for investigating the patients with UC with thrombotic complications for other thrombophilic states.

EUS versus endoscopic retrograde cholangiography for patients with intermediate probability of bile duct stones: a prospective randomized trial.

BACKGROUND: Factors affecting diagnostic accuracy and comparison of patients in the follow-up period for negative outcomes are not thoroughly investigated in a randomized trial. OBJECTIVE: Our purpose was to compare diagnostic accuracy, complications, and number of interventions. DESIGN: Prospective, unicentric, single-blind, randomized study. SETTING: Single tertiary referral university hospital. PATIENTS: One hundred twenty patients with intermediate risk for common bile duct (CBD) stones were randomized to either an EUS-first, endoscopic retrograde cholangiography (ERC)-second (n = 60) versus an ERC-only (n = 60) procedure. INTERVENTIONS: EUS, ERC, sphincterotomy, and balloon sweeping of CBD when needed. MAIN OUTCOME MEASUREMENTS: Sensitivity of EUS versus ERC, factors affecting diagnostic capability, complications, total number of endoscopic procedures. RESULTS: The sensitivity and specificity of ERC were 75% (95% CI, 42%-93%) and 100% (95% CI, 95%-100%), respectively. The sensitivity and specificity of EUS were 91% (95% CI, 59%-99%) and 100% (95% CI, 95%-100%), respectively. EUS is more sensitive than ERC in detecting stones smaller than 4 mm (90% vs 23%, P < .01). Although not significant, there was a trend for an increased number of endoscopic procedures in the ERC group compared with the EUS group (98 vs 83). The post-ERC pancreatitis rate was 6 in 120 (5%) in all study patients, and the post-ERC pancreatitis rate in patients with an undilated CBD was 5 of 53 (9.43%). The independent factors for post-ERC pancreatitis are undilated CBD (risk ratio [RR] 6.320; 95% CI, 1.703-11.524, P = .009), allocation into the ERC group (RR 2.107; 95% CI, 1.330-3.339, P = .02), female sex (RR 1.803; 95% CI, 1.155-2.813, P = .03), and age less than 40 years (RR 1.888; 95% CI, 1.245-2.863, P = .01). Kaplan-Meier analysis revealed higher rate of negative outcome in the ERC group than in the EUS group (P = .049, log-rank test). CONCLUSION: The EUS-first approach is not associated with further risk for subsequent endoscopic procedures. Patients with an undilated CBD should be investigated by the EUS-first approach to prevent post-ERC pancreatitis.

Could the simplified (14)C urea breath test be a new standard in noninvasive diagnosis of Helicobacter pylori infection?

OBJECTIVE: The carbon-14 ((14)C) urea breath test (UBT) is a reliable and noninvasive technique for the diagnosis of Helicobacter pylori (HP) infection. The diagnostic performance of a new practical and low dose (14)C UBT system (Heliprobe, Stockholm, Sweden) was compared with those of other diagnostic tests, namely, rapid urease test (RUT), histopathology, and DNA detection using polymerase chain reaction (PCR). METHODS: Eighty-nine patients (mean age = 45 +/- 13, 30 men) with dyspeptic complaints who underwent an endoscopic procedure were studied. Biopsy specimens acquired during the procedure were subjected to RUT, histopathological examination using hematoxylin and eosin (HP-HE) and PCR. All patients underwent UBT using the Heliprobe system on a different day. The gold standard for HP positivity was defined as any two of the three tests being positive, excluding UBT, and the sensitivity and specificity of any single test alone were determined using this gold standard. Whenever only one test was positive, it was considered to be a false-positive one. RESULTS: With the gold standard used in this study, 59 (66%) patients were diagnosed HP positive. The Heliprobe method detected HP infection with 96.6% sensitivity and 100% specificity and had the best diagnostic performance when compared with all the other methods. The sensitivity and specificity of the other methods for the detection of HP positivity were 89.8% and 100% for RUT, 93.2% and 63.3% for PCR, and 93.2% and 76.6% for HP-HE, respectively. Areas under the receiver-operating characteristic were 0.977 for UBT, 0.947 for RUT, 0.84 for HP-HE, and 0.775 for PCR. CONCLUSIONS: Using a combination of invasive diagnostic tests as the gold standard, Heliprobe UBT was found to be highly sensitive and specific for the diagnosis of HP infection in patients with dyspeptic complaints.

Esomeprazole in acute and maintenance treatment of reflux oesophagitis: a multicentre prospective study.

INTRODUCTION: The aim of this study was to assess the efficacy and safety of esomeprazole 40 mg once daily (q.d.) in healing reflux oesophagitis at 4 and 8 weeks, and the efficacy of esomeprazole 20 mg q.d. for 12 weeks in the maintenance of remission. METHODS: A total of 235 patients with endoscopically proven reflux oesophagitis were enrolled in this study, which consisted of two phases (healing and maintenance therapy). Patients who showed complete endoscopic and symptomatic healing at the end of 4 or 8 weeks were switched to maintenance treatment with esomeprazole 20 mg q.d. for 12 weeks. The primary efficacy endpoint was healing of reflux oesophagitis at week 8. Secondary assessments included the proportion of patients with symptomatic relapse in the maintenance phase. RESULTS: At the end of week 8, 88% (95% life-table confidence intervals [CI]: 84%, 92%) of patients were healed endoscopically and 90.6% of the patients were asymptomatic. Patient age, gender and Helicobacter pylori status had no effect on the efficacy of treatment. During the 12-week maintenance treatment phase, symptomatic relapse ratios were 0.5%, 2.2%, and 0%, for the first, second, and third 4-week periods, respectively. The proportions of patients satisfied with treatment were 95% and 99.4% at the end of acute and maintenance treatment, respectively. The most common adverse effects were headache, upper respiratory tract infection and abdominal pain. CONCLUSIONS: Esomeprazole is effective in the healing of reflux oesophagitis, the resolution of heartburn, and in maintaining symptomatic remission. The effectiveness of esomeprazole in patients with gastroesophageal reflux disease is not affected by the presence of H. pylori.

The relationship between the MEFV genotype, clinical features, and cytokine-inflammatory activities in patients with familial mediterranean fever.

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period. White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.

Small-volume gallbladders and decreased motility in patients with achalasia.

AIM/BACKGROUND: Achalasia may be associated with extraesophageal dysmotility. However, this relation is still poorly understood. In the present study, we used noninvasive real-time ultrasonography to examine the motility function of the gallbladder in the patients with achalasia. MATERIALS AND METHODS: Thirty-three achalasic patients and 33 healthy volunteers were included in the study. All subjects were investigated after 12 hours of fasting and 30 minutes after a standard test meal. Premeal and postmeal gallbladder volumes were used for calculation of the ejection fraction of the gallbladder and fasting gallbladder volume. RESULTS: The mean fasting volume (18.52+/-1.45 vs. 24.63+/-1.84 cm; P<0.05) and ejection fractions of gallbladder (35.84+/-4.12 vs. 54.47+/-2.47; P<0.05) in the patients with achalasia were lower than the control group. CONCLUSIONS: Such a finding may confirm the possible extraesophageal extension of primary achalasia. Achalasic patients have smaller gallbladders than do others. It could be speculated that it is congenital and/or achalasic patients' gallbladder has incomplete relaxation (as in the lower esophageal sphincter of the achalasia).

Identification of Helicobacter species by 16S rDNA PCR and sequence analysis in human liver samples from patients with various etiologies of benign liver diseases.

BACKGROUND/AIMS: Several reports indicated an increased prevalence of the Helicobacter species in hepatocellular cancer tissue and in liver samples infected with hepatitis viruses. The frequency of Helicobacter spp. in benign liver diseases was, however, not thoroughly investigated. METHODS: Seventy-five consecutive patients with suspected liver disease were enrolled. The indications were hepatitis B virus (n=30), C virus (n=8), B and C dual infection (n=1), nonalcoholic steatohepatitis (n=27), autoimmune hepatitis (n=3), primary biliary cirrhosis (n=1) and idiopathic elevation of liver enzymes (n=5). PCR detection of 16S recombinant RNA gene of Helicobacter spp. was performed on liver samples. PCR products of positive samples were further identified by DNA sequencing. The patients also had upper gastrointestinal endoscopy and gastric biopsy for the detection of H. pylori using histopathology and PCR. RESULTS: Helicobacter spp. DNA was detected in two out of 75 liver biopsy samples (2.6%), which were typed as H. pylori by DNA sequencing. One of these patients had chronic hepatitis C infection (man, 51 years old) and the other had nonalcoholic steatohepatitis (woman, 44 years old). Fifty-two out of 75 of the patients (69.3%) had H. pylori infection in their stomachs. CONCLUSION: We have found that H. pylori infection is much less prevalent in benign liver diseases. The presence of H. pylori in nonalcoholic steatohepatitis (NASH) patients is a novel finding and this finding should be confirmed in a larger series.