Insulin Resistance as a Novel Risk Factor for Post-ERCP Pancreatitis: A Pilot Study.

BACKGROUND AND AIMS: The relationship between insulin resistance and post-ERCP pancreatitis (PEP) is not known. We aimed to determine the relation between pre-ERCP insulin resistance and risk of PEP, and to evaluate the relationship of insulin resistance with well-established risk factors for PEP. METHODS: Consecutive patients who underwent ERCP with the diagnosis of choledocolithiasis between January and December 2013 were enrolled in this prospective study. Pre-procedural insulin resistance state and other risk factors were evaluated according to PEP development. RESULTS: Pancreatitis developed in 16 (11.3 %) of 141 ERCP procedure. Homeostasis model assessment of insulin resistance (HOMA-IR) levels was found statistically significantly higher in patients who developed PEP than the ones who did not (3.37 ± 0.8 vs. 2.38 ± 1.4, p < 0.001). Common bile duct (CBD) diameter of the patients developing PEP was found significantly lower than the non-PEP group (10.1 ± 4 vs. 13.4 ± 4.5 mm, p = 0.01). Mean procedure time was 33.5 min in PEP group and 27.9 min in non-PEP group (p = 0.006). HOMA-IR (OR 2.39), procedure time (OR 1.15), and CBD diameter (OR 0.82) were independent predictors of PEP development. CONCLUSIONS: The presence of insulin resistance is an important risk factor for PEP, and these data can be used as a considerable clue to predict the risk of PEP before ERCP and to decrease related morbidity.

Effect of Entecavir and Tenofovir Treatment on Noninvasive Fibrosis Scores: Which One Is Better?

Liver biopsy is the best method for detecting fibrosis grade of the liver in chronic hepatitis B. However, the invasiveness of liver biopsy complicates its routine use in follow-up of treatment. We planned to determine the usage of fibrosis predicting noninvasive scores in the follow-up of the treatment of patients with chronic hepatitis B treated with entecavir or tenofovir. Two hundred twenty-eight patients with hepatitis B with liver biopsy were included in the study. Fibrosis grade was determined by Ishak score. The laboratory data at months 0, 12, and 24 during treatment were collected and noninvasive fibrosis scores (aspartate aminotransferase to alanine aminotransferase ratio [AAR], aspartate aminotransferase to platelet ratio index [APRI], fibrosis index based on the 4 factors [FIB-4] and red cell distribution width to platelet ratio [RPR]) were calculated. Statistically significant increase in all scores and decrease in platelet count were observed as the fibrosis level increased. For differentiation of patients with fibrosis ≥grade 2, the highest sensitivity and specificity rates were shown by APRI score (sensitivity 67%, specificity 69%, and cutoff ≥0.5). FIB-4 was the most successful score for differentiation of patients with fibrosis ≥grade 3 (sensitivity 83%, specificity 74%, and cutoff ≥1.45). A significant decrease in all noninvasive fibrosis scores was observed at months 12 and 24 during treatment with both entecavir and tenofovir (P < 0.001). Among these, only the improvement in APRI score was found better in entecavir group with statistical significance (P < 0.05). APRI score was effective in demonstrating early-stage fibrosis. FIB-4, RPR, and platelet count were better in demonstrating advanced fibrosis. Although noninvasive scores cannot replace liver biopsy for diagnosis, they can be used for monitoring the response to treatment.

First Week HCV RNA Level Under the Pegylated Interferon and Ribavirin Treatment Predicts Sustained Virological Response.

This study was planned to investigate whether the decrease in the hepatitis C virus (HCV) RNA levels at the first week of combined pegylated interferon and ribavirin treatment of naive genotype 1 patients with HCV was predicting sustained virologic response (SVR). Fifty-two patients were enrolled into the study. HCV RNA levels were measured at the baseline, first, fourth, and 12th weeks of treatment. Thirty-four patients achieved SVR, which basal, first week, and fourth week HCV RNA levels were log 5.57, log 3.65, and log 1.92, respectively. Eighteen patients could not achieve SVR, which basal, first week, and fourth week HCV RNA levels were log 6.22, log 5.45, and log 3.84, respectively (P < 0.05). Patients were distributed in 2 groups according to the amount of decrease in HCV RNA levels at the first week as less or more than 1.5 log. There were 20 patients with ≥1.5 log decrease in the HCV RNA levels at the first week. They were named as patients with very rapid virologic response (VRVR). All patients (100%) with VRVR were achieved SVR. In only 14 (44%) of the 32 patients without VRVR, SVR was achieved. In 16 (84%) of the 19 patients with rapid virologic response and 33 (79%) of the 42 patients with early virologic response, SVR was achieved. A ≥1.5 log decrease (VRVR) in HCV RNA levels of patients with HCV at the first week of combined pegylated interferon and ribavirin treatment predicts SVR very strongly.

Plasma Pentraxin 3 Differentiates Nonalcoholic Steatohepatitis (NASH) from Non-NASH.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a variety of histopathological findings ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which can only be differentiated by liver biopsy. There is yet no unique biomarker found to discriminate NASH from simple steatosis.We aimed to investigate the relationship of plasma pentraxin 3 (PTX3) and its main stimulant tumor necrosis factor alpha (TNF-α) with the degree of liver damage in NAFLD. METHODS: Plasma PTX3 and TNF-α levels were measured in 70 patients with histologically verified NAFLD (56 with NASH, 14 with non-NASH) and 12 controls. RESULTS: PTX3 and TNF-α levels were found significantly higher in the NAFLD group than in the control group (4.1 ± 2.3 vs. 1.3 ± 0.8 ng/mL, P < 0.001, and 7.6 ± 4.1 vs. 3.3 ± 1.3 pg/mL, P < 0.001 respectively) and in biopsy proven NASH subgroup than non-NASH subgroup (4.6 ± 2.2 vs. 2.2 ± 1.7 ng/mL, P = 0.001, and 8.3 ± 4.3 vs. 4.6 ± 1.6 pg/mL, P = 0.001 respectively). To discriminate NASH from non-NASH PTX3 had 91.1% sensitivity and 71.4% specificity at the cutoff value of 2.45 ng/mL. Plasma PTX3 levels showed correlation with NAFLD activity score, fibrosis stage and steatosis grade (r = 0.659, P < 0.001; r = 0.354, P < 0.01; and r = 0.455, P < 0.001, respectively). CONCLUSION: This study demonstrated markedly higher PTX3 levels in NAFLD patients compared with controls, and in biopsy proven NASH patients compared with non-NASH ones. Thus, in this cohort we showed that plasma PTX3 may be a promising biomarker for the presence of NASH.

Increased Plasma Levels of Asymmetric Dimethylarginine in Nonalcoholic Fatty Liver Disease: Relation With Insulin Resistance, Inflammation, and Liver Histology.

BACKGROUND AND AIM: Cardiovascular disease (CVD) is the most frequent cause of death in nonalcoholic fatty liver disease (NAFLD). Insulin resistance, hepatic dysfunction, and chronic inflammation are factors interacting in explaining the increased CVD incidence in NAFLD. We aimed to evaluate the effects of insulin resistance and inflammatory biomarkers on asymmetric dimethylarginine (ADMA) levels, a predictor of CVD. We also investigated relationship between these markers and histological findings in patients with NAFLD. PATIENTS AND METHODS: Plasma ADMA, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured in 70 patients with histologically verified NAFLD (53 with nonalcoholic steatohepatitis [NASH], 17 with non-NASH) and 12 controls. RESULTS: The HOMA-IR (5.3 [3.9] vs 1.9 [1], P < 0.001), hs-CRP (5.6 [4.2] vs 2.2 [2.3] mg/L, P < 0.001), ADMA (0.81 [0.25] vs 0.48 [0.24] µmol/L, P = 0.005), and IL-6 (4.1 [1.2] vs 1.0 [0.4] pg/mL, P < 0.001) levels were all found higher in the NAFLD group than the control group. The ADMA levels were significantly higher in patients with NAFLD independent from HOMA-IR and body composition (P = 0.02). The IL-6 and HOMA-IR levels of the NASH group were found significantly higher than those of the non-NASH group. The only determinant significantly correlated to ADMA was HOMA-IR. CONCLUSIONS: Our data suggested that although ADMA levels are independently higher in NAFLD, the only determinant correlated to ADMA is HOMA-IR and not inflammatory biomarkers (hs-CRP, IL-6) or presence/absence of NASH.

Diagnostic and Therapeutic Roles of Endoscopic Ultrasound in Pediatric Pancreaticobiliary Disorders.

OBJECTIVES: The diagnostic role of endoscopic ultrasound (EUS) in children has only recently been demonstrated, and that also to a lesser extent than in adults. Data on the technique's therapeutic indications remain scarce. We therefore sought to evaluate diagnostic and interventional EUS indications, safety, and impact in children with pancreaticobiliary disorders. METHODS: We retrospectively reviewed our single pediatric center records, covering a 14-year period. RESULTS: From January 2000 to January 2014, 52 EUS procedures were performed in 48 children (mean age: 12 years; range: 2-17 years) with pancreaticobiliary disorders for the following indications: suspected biliary obstruction (n = 20/52), acute/chronic pancreatitis (n = 20), pancreatic mass (n = 3), pancreatic trauma (n = 7), and ampullary adenoma (n = 2). EUS was found to have a positive impact in 51 of 52 procedures, enabling us to avoid endoscopic retrograde cholangiopancreatography (ERCP) (n = 13 biliary; n = 6 pancreatic), focusing instead on endotherapy (n = 7 biliary; n = 14 pancreatic) or reorienting therapy toward surgery (n = 7). EUS-guided fine-needle aspiration was carried out on 12 patients for pancreatic tumor (n = 4), pancreatic cyst fluid analysis (n = 4), autoimmune pancreatitis (n = 2), and suspicion of biliary tumor (n = 2). A total of 13 therapeutic EUS procedures (11 children) were conducted, including 9 combined EUS-ERCP procedures (7 children, mean age: 8 years, range: 4-11 years), 3 EUS-guided pseudocyst drainage (2 children), and 1 EUS-guided transgastric biliary drainage. CONCLUSIONS: Our study reports on a large pediatric EUS series for diagnostic and therapeutic pancreaticobiliary disorders, demonstrating the impact of diagnostic EUS and affording insights into novel EUS and combined EUS-ERCP therapeutic applications. We suggest considering EUS as a diagnostic and therapeutic tool in the management of pediatric pancreaticobiliary diseases.

How does a biopsy of endoscopically normal terminal ileum contribute to the diagnosis? Which patients should undergo biopsy?

BACKGROUND: Terminal ileum endoscopy and biopsy are the diagnostic tools of diseases attacking the ileum. However, abnormal histological findings can be found in endoscopically normal terminal ileum. OBJECTIVE: This study was performed to evaluate the histopathological results of biopsies from endoscopically normal terminal ileum in order to determine pre-procedure clinical and laboratory factors predicting abnormal histopathological results, if any. METHODS: A total of 297 patients who underwent colonoscopy and terminal ileum biopsy and had normal terminal ileum or a few aphthous ulcers in the terminal ileum together with completely normal colon mucosa were included in the study. The patients were grouped into two arms as normal cases and cases with aphthous ulcers. Histopathological and pre-procedural laboratory results of patients were analyzed according to their indications. RESULTS: The terminal ileum was endoscopically normal in 200 patients, and 97 patients had aphthous ulcers. Chronic ileitis rate was present in 5.5% of those with endoscopically normal terminal ileum and in 39.2% of the patients with aphthous ulcers. In both groups, the highest rate of chronic ileitis was detected in the patients with known inflammatory bowel disease (IBD) (15.4 and 50%, respectively), anemia (9.5 and 43.5%, respectively), and in the patients having chronic diarrhea together with abdominal pain (7.7 and 44.8%, respectively). We found that the sensitivity of mean platelet volume for predicting chronic ileitis was 87% and the specificity was 45% at a cut-off value lower than 9.35 fl. CONCLUSION: In anemia indication or chronic diarrhea together with abdominal pain, the frequency of aphthous ulcers detected by ileoscopy and the frequency of chronic ileitis detected histopathologically despite a normal-appearing ileum were elevated.

Increased prevalence of colorectal polyp in acromegaly patients: a case-control study.

An increase in the prevalence of colorectal polyps and cancer is reported in patients with acromegaly. This trial is designed to determine whether there is an increase in the prevalence of colorectal polyps/cancer in Turkish acromegaly patients. Sixty-six patients, who were under follow-up with the diagnosis of acromegaly and underwent total colonoscopic examination, were enrolled in the study. Sixty-five age- and gender-matched patients with nonspecific complaints were selected as control. The mean age of acromegalic patients was 51.5 ± 12.8 years of whom 27 (40.9%) were females. In 20 (30.3%) of the patients with acromegaly a total of 65 colorectal polyps were detected. Forty-seven (72.3%) of the polyps were detected at the rectosigmoid region. In 8 (12.3%) of the 65 control patients a total of 17 polyps were found. There was a statistically significant difference between the groups (P = 0.018). At the logistic regression analysis we found that the risk for colon polyps increased 3.2-fold in the presence of acromegaly, irrespective of age and gender (OR: 3.191, 95% CI: 1.25-8.13). In conclusion, patients who were followed up with the diagnosis of acromegaly should be taken to the colonoscopic surveillance program and all polyps detected should be excised in order to protect them from colorectal cancer.

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.

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.

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).

The rare presentations of a large polyp and an esophageal carcinoma in heterotropic gastric mucosa: a case series.

BACKGROUND: Heterotopic gastric mucosa (HGM) is commonly seen in the upper esophagus during endoscopyand is generally considered a benign disease. A hyperplastic polyp and an adenocarcinoma arising in heterotopic gastric mucosa are quite rare occurences. CASE PRESENTATIONS: We present two cases: The first is a patient who suffered from dysphagia because of a large hyperplastic polyp that arose from HGM; the polyp was excised endoscopically. Secondly, we report a rare case of adenocarcinoma arising in HGM of the cervical esophagus. CONCLUSION: Morphologic changes or malignant transformation can develop in the inlet patch. Therefore, gastroenterologists should be aware of the possibility of HGM just distal to the upper esophageal sphincter.

Acute hepatitis induced by Epstein-Barr virus infection: a case report.

Epstein-Barr virus is a causative agent of infectious mononucleosis syndrome, which is commonly seen in young adults and characterized by fever, sore throat and lymphadenopathy. In adults, Epstein-Barr virus infection can cause liver function test abnormalities without pharyngitis or lymphadenopathy. Liver involvement usually causes mild elevation of transaminases and this abnormality resolves spontaneously. Jaundice might develop rarely during the clinical course of Epstein-Barr virus infection. It reflects either more severe hepatitis or Epstein-Barr virus infection-associated hemolytic anemia. Acute hepatitis with icterus is a rare clinical manifestation in primary Epstein-Barr virus infection. Especially in older patients, Epstein-Barr virus infection can cause cholestasis; the diagnosis can be established by elimination of extrahepatic biliary obstruction. Here we report an acute hepatitis in a patient who presented with icterus and was diagnosed as acute Epstein-Barr virus infection.

Comparison of early enteral nutrition in severe acute pancreatitis with prebiotic fiber supplementation versus standard enteral solution: a prospective randomized double-blind study.

AIM: To compare the beneficial effects of early enteral nutrition (EN) with prebiotic fiber supplementation in patients with severe acute pancreatitis (AP). METHODS: Thirty consecutive patients with severe AP, who required stoppage of oral feeding for 48 h, were randomly assigned to nasojejunal EN with or without prebiotics. APACHE II score, Balthazar's CT score and CRP were assessed daily during the study period. RESULTS: The median duration of hospital stay was shorter in the study group [10 +/- 4 (8-14) d vs 15 +/- 6 (7-26) d] (P < 0.05). The median value of days in intensive care unit was also similar in both groups [6 +/- 2 (5-8) d vs 6 +/- 2 (5-7) d]. The median duration of EN was 8 +/- 4 (6-12) d vs 10 +/- 4 (6-13) d in the study and control groups, respectively (P > 0.05). Deaths occurred in 6 patients (20%), 2 in the study group and 4 in the control group. The mean duration of APACHE II normalization (APACHE II score < 8) was shorter in the study group than in the control group (4 +/- 2 d vs 6.5 +/- 3 d, P < 0.05). The mean duration of CRP normalization was also shorter in the study group than in the control group (7 +/- 2 d vs 10 +/- 3 d, P < 0.05). CONCLUSION: Nasojejunal EN with prebiotic fiber supplementation in severe AP improves hospital stay, duration nutrition therapy, acute phase response and overall complications compared to standard EN therapy.